Chylous plasma recovery process

Abstract

The application provides a chylomicron plasma recovery treatment method, in which kaolin is modified by alkali and acid substances in sequence, and then the modified kaolin and diatomite are used to filter chylomicron plasma in sequence, and a filter with a multilayer gradient structure is used when the diatomite is used to treat chylomicron plasma; by the technical scheme, the cholesterol and triglyceride in the chylomicron plasma are significantly reduced, and a plasma product with low turbidity is obtained.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chylomicron plasma recovery processing, and particularly relates to a chylomicron plasma recovery processing method. BACKGROUND

[0002] Human plasma resources are very valuable, but at present, a part of blood donors have high blood lipids, causing the plasma to be highly turbid, and thus cannot be used for clinical application and plasma protein production to obtain albumin and globulin resources.

[0003] Therefore, how to efficiently reduce the turbidity of chylomicron plasma to obtain a plasma product with better quality needs to be researched. SUMMARY

[0004] The present application aims to provide a chylomicron plasma recovery processing method to reduce the turbidity of chylomicron plasma, thereby obtaining a plasma product with better quality.

[0005] To achieve the above-mentioned purpose, the present application provides the following technical scheme:

[0006] A chylomicron plasma recovery processing method, the method comprising the following steps:

[0007] S1, providing modified kaolin;

[0008] S2, mixing the modified kaolin obtained in step S1 with chylomicron plasma;

[0009] S3, filtering the material obtained in step S2 to obtain recovered plasma;

[0010] In the step S1, the modified kaolin is obtained by the following method:

[0011] A1, providing kaolin;

[0012] A2, treating the kaolin obtained in step A1 with alkali;

[0013] A3, treating the kaolin obtained in step A2 with acid;

[0014] In the step S3, a filter with a multi-layer gradient structure using diatomite as the adsorption medium is used for the filtering operation.

[0015] Other applicable fields will become apparent from the description provided in the present disclosure.

[0016] The description in the summary and specific examples are only intended to illustrate and are not intended to limit the scope of the present disclosure.

[0017] Compared with the prior art, the technical scheme provided by the present application has the following beneficial effects:

[0018] This invention modifies kaolin sequentially with alkali and acidic substances, and then uses the modified kaolin and diatomaceous earth to filter chylous plasma. A multi-layered gradient filter is also used when processing chylous plasma with diatomaceous earth. Through the above technical solution, this invention significantly reduces cholesterol and triglycerides in chylous plasma, resulting in plasma products with lower turbidity. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other solutions can be obtained based on these drawings without creative effort.

[0020] Figure 1 This is a flowchart illustrating a method for recovering and processing chylous plasma according to an embodiment of the present invention. Detailed Implementation

[0021] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. It should be understood that the specific embodiments described herein are only for illustration and explanation of the present invention and are not intended to limit the present invention.

[0022] Any specific numerical values ​​disclosed herein (including the endpoints of numerical ranges) are not limited to their exact values, but should be understood to also include values ​​close to the exact value, such as all possible values ​​within ±5% of the exact value. Furthermore, with respect to the disclosed numerical ranges, one or more new numerical ranges can be obtained by arbitrarily combining the endpoint values ​​of the range, the endpoint values ​​with specific point values ​​within the range, and the specific point values ​​themselves; these new numerical ranges should also be considered as specifically disclosed herein.

[0023] The terminology used in this disclosure is for the purpose of describing particular exemplary embodiments only and is not intended to be limiting. Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” as used in this disclosure are intended to include the plural forms as well. The terms “comprising,” “including,” “containing,” and “having” are inclusive and thus describe the presence of said features, elements, compositions, steps, integers, operations, and / or components, but do not exclude the presence or inclusion of one or more other features, integers, steps, operations, elements, components, and / or sets thereof. Although the open-ended term “comprising” should be understood as a non-limiting term used to describe and claim the various embodiments described in this disclosure, in some aspects it may instead be understood as a more restrictive and limiting term, such as “consisting of” or “substantially consisting of.” Thus, for any given embodiment describing a composition, material, component, element, feature, integer, operation, and / or process step, this disclosure also particularly includes embodiments consisting of or substantially consisting of such compositions, materials, components, elements, features, integers, operations, and / or process steps. In the case of “consisting of…”, the alternative embodiments exclude any additional compositions, materials, components, elements, features, integers, operations and / or process steps. In the case of “essentially composed of…”, any additional compositions, materials, components, elements, features, integers, operations and / or process steps that substantially affect the essential and novel characteristics are excluded from such embodiments. However, any compositions, materials, components, elements, features, integers, operations and / or process steps that do not substantially affect the essential and novel characteristics may be included in the embodiments.

[0024] Any method steps, processes, and operations described in this disclosure should not be construed as necessarily requiring them to be performed in a particular order as discussed or shown, unless explicitly specified. It should also be understood that additional or alternative steps may be used unless otherwise stated.

[0025] In this application, except where expressly stated, any matters or issues not mentioned are directly applicable to those known in the art without any modification. Furthermore, any implementation described in this disclosure may be freely combined with one or more other implementations described in this disclosure, and the resulting technical solutions or concepts shall be considered part of the original disclosure or original record of this application, and should not be regarded as new content not disclosed or anticipated in this disclosure, unless those skilled in the art consider the combination to be clearly unreasonable.

[0026] Unless otherwise stated, the terms used herein have the same meaning as commonly understood by those skilled in the art, and if a term is defined herein and its definition differs from the common understanding in the art, the definition herein shall prevail.

[0027] Unless otherwise stated, when % is mentioned in this document, it refers to wt%.

[0028] See Figure 1 This invention provides a method for recovering chylous plasma, comprising the following steps: S1, providing modified kaolin; S2, mixing the modified kaolin obtained in step S1 with chylous plasma; S3, filtering the material obtained in step S2 to obtain recovered plasma; wherein, the modified kaolin in step S1 is obtained by the following methods: A1, providing kaolin; A2, treating the kaolin obtained in step A1 with alkali; A3, treating the kaolin obtained in step A2 with acid; wherein, in step S3, a filter with diatomaceous earth as the adsorption medium and having a multi-layer gradient structure is used to perform the filtration operation.

[0029] It is worth noting that the present invention modifies kaolin by sequentially using alkali and acidic substances, and then uses the modified kaolin and diatomaceous earth to filter chylous plasma. In the process of using diatomaceous earth to treat chylous plasma, a filter with a multi-layer gradient structure is also used. Through the above technical solution, the present invention significantly reduces cholesterol and triglycerides in chylous plasma, and obtains plasma products with lower turbidity.

[0030] It should be noted that the layered structure of kaolin (chemical formula Al2Si2O5(OH)4) provides a large number of adsorption sites, but activation is required to improve its performance. The purpose of alkali treatment of kaolin is to remove impurities and expose the Al-OH active sites of kaolin to achieve efficient adsorption. Specifically, alkali treatment can dissolve amorphous silica and some metal oxides. The purpose of acid treatment of kaolin is to neutralize the residual alkali solution from the previous alkali treatment, stabilize the interlayer structure of kaolin, and adjust the surface charge of kaolin. The alkali-acid treatment first results in higher adsorption capacity and selective adsorption of kaolin. Specifically, alkali treatment can increase the specific surface area of ​​kaolin, while acid treatment can optimize the surface charge distribution of kaolin to achieve selective adsorption.

[0031] It is understood that this invention achieves efficient recovery and treatment of chylous plasma through a series of steps, and there is a clear causal relationship between the technical features of each step and the final effect: First, in step S1, kaolin is functionalized through a continuous modification process of alkali treatment and acid treatment. Alkali treatment can expand the interlayer distance of kaolin and activate surface hydroxyl groups, while the subsequent acid treatment further increases its specific surface area and porosity. This dual modification gives kaolin a stronger adsorption capacity, especially a specific binding capacity for lipids. When this modified kaolin is mixed with chylous plasma in step S2, its surface properties can selectively capture chylomicrons in the plasma, effectively adsorbing lipids such as cholesterol and triglycerides. In step S3, a multi-layer gradient structure filter with diatomaceous earth as the adsorption medium is used for fine filtration. The porous nature of diatomaceous earth can achieve deep interception of residual small lipoproteins, while the multi-layer gradient design intercepts larger particles and then captures fine impurities through a step-by-step filtration mechanism. This synergistic effect significantly improves filtration efficiency. The resulting recovered plasma not only has a significantly reduced lipid content but also significantly improved turbidity. In the entire recovery process, the pretreatment with modified kaolin and the post-processing fine filtration with diatomaceous earth complement each other. The former is mainly responsible for the removal of the main lipids, while the latter completes the fine purification process. The sequential combination of the two and the setting of special treatment conditions jointly contribute to the dual improvement of the purity and clarity of the plasma product.

[0032] In some embodiments of the present invention, in step A1, the D50 of the kaolin is 1-10 μm. It should be noted that controlling the D50 (median particle size) of the kaolin within the range of 1-10 μm can significantly optimize its adsorption effect on lipids in chylous plasma. A smaller particle size (1-10 μm) gives the kaolin a larger specific surface area and more active sites, thereby enhancing its contact efficiency with chylomicrons, cholesterol, and triglycerides in plasma and improving its adsorption capacity. Simultaneously, this particle size range ensures good dispersibility of the kaolin particles in plasma, avoiding excessively rapid sedimentation, and also prevents the filter membrane from clogging or affecting the filtration speed in subsequent filtration steps due to excessively fine particles. Furthermore, a suitable particle size also ensures the uniformity of the modification treatment (alkali treatment and acid treatment), allowing the surface activity and pore structure of the kaolin to be fully optimized, further improving its lipid removal efficiency. Therefore, this preferred embodiment enables modified kaolin to achieve optimal adsorption performance and operational stability during chylous plasma treatment, ultimately resulting in recovered plasma with higher purity and lower turbidity. For example, the D50 of the kaolin can be any value selected from 2μm, 3μm, 4μm, 5μm, 6μm, 7μm, 8μm, or 9μm, or any value within a range consisting of any two of these values.

[0033] In some embodiments of the present invention, in step A1, the D90 of the kaolin is less than or equal to 20 μm. It is worth noting that by controlling the D90 of the kaolin to ≤20 μm (i.e., 90% of the kaolin particles have a diameter not exceeding 20 μm), the treatment effect of chylous plasma can be further improved, specifically in the following aspects: First, this particle size limitation ensures the overall uniformity of the kaolin particles, avoiding the influence of a small number of excessively large particles (e.g., >20 μm) on the uniformity of the modification treatment; since the effects of alkali and acid treatments are closely related to the specific surface area of ​​the particles, excessively large particles may lead to incomplete surface modification, reducing the subsequent adsorption capacity for lipids; second, the setting of D90 ≤20 μm further... The suspension stability of kaolin in plasma was optimized, allowing it to disperse more uniformly in chylous plasma, thereby increasing contact opportunities with chylomicrons, cholesterol, and triglycerides and improving adsorption efficiency. Simultaneously, this particle size range still maintains good filtration performance, avoiding clogging or reduced filtration speed of subsequent diatomaceous earth filters due to excessively fine particles (e.g., too small D90). Furthermore, this preferred scheme enhances process controllability and repeatability, as kaolin with a narrower particle size distribution exhibits greater stability during modification, mixing, and filtration, ultimately contributing to recovered plasma with lower turbidity and higher lipid removal rates. Therefore, setting D90 ≤ 20 μm ensures adsorption performance while also considering process feasibility and plasma product quality stability. For example, the D90 of the kaolin can be any value from 12 μm, 13 μm, 14 μm, 15 μm, 16 μm, 17 μm, 18 μm, or 19 μm, or any value within a range consisting of any two of these values.

[0034] In some embodiments of the present invention, in step A1, the specific surface area of ​​the kaolin is 10~50m². 2 / g. It should be noted that the specific surface area of ​​kaolin should be controlled between 10 and 50 m². 2 Within the range of 10–50 m² / g, it can significantly improve its adsorption efficiency and selectivity for lipids in chylous plasma. This specific surface area range works through several key mechanisms: firstly, 10–50 m² / g... 2 A specific surface area of ​​ / g ensures that kaolin has a sufficiently abundant number of surface active sites, allowing it to fully expose more hydroxyl groups and surface charge sites during alkali and acid treatment modifications. These active sites can form strong physical adsorption and chemical interactions with cholesterol and triglyceride molecules in chylomicrons, thereby improving lipid removal rates. Secondly, this specific surface area range achieves an optimal balance between adsorption capacity and mass transfer efficiency. Too low a specific surface area (<10m²) would be detrimental. 2 A specific surface area of ​​50 m² / g can lead to insufficient adsorption sites, affecting lipid removal efficiency; while an excessively high specific surface area (>50 m² / g) can lead to insufficient adsorption sites, affecting lipid removal efficiency. 2While theoretically, kaolinite ( / g) has a stronger adsorption capacity, in practical applications it may lead to particle aggregation and decreased dispersibility, thus reducing the probability of effective contact with lipoproteins in plasma. Furthermore, this specific surface area range has a synergistic effect with a D50 particle size of 1-10 μm and a particle size distribution of D90≤20 μm. A moderate specific surface area ensures that the modified kaolinite maintains good suspension stability in plasma without causing particle aggregation due to excessive surface energy, ensuring smooth separation during subsequent diatomaceous earth gradient filtration. Ultimately, this optimal solution allows the modified kaolinite to maintain excellent adsorption performance while considering process feasibility and processing efficiency, providing a key guarantee for obtaining high-quality recovered plasma with low turbidity and low lipid content. For example, the specific surface area of ​​the kaolinite can be 15 m². 2 / g、20m 2 / g、25m 2 / g、30m 2 / g、35m 2 / g、40m 2 / g or 45m 2 Any value in / g or any value within a range of any two values.

[0035] In some embodiments of the present invention, in step A1, the porosity of the kaolin is 40-60%. It is understood that controlling the porosity of the kaolin within the range of 40-60% can significantly optimize its treatment efficiency for chylous plasma at the microstructural level. This porosity characteristic works through multiple synergistic mechanisms: First, the medium-high porosity of 40-60% provides an ideal structural basis for subsequent alkali-acid modification treatment. This porosity range ensures sufficient internal channels for the penetration of modifying reagents (alkali and acid solutions), allowing for sufficient exfoliation and activation of the kaolin's layered structure, while avoiding the problem of decreased mechanical strength caused by excessively high porosity. After modification, this moderate porosity structure can form more abundant mesopores (2~50 nm), which perfectly matches the size characteristics of chylomicrons (50~1000 nm), achieving a dual effect of efficient size sieving and surface adsorption. Secondly, this porosity range creates an optimal mass transfer-adsorption balance. When the porosity is below 40%, the effective internal adsorption area is insufficient, affecting lipid retention efficiency; while above 60%, although the adsorption capacity increases, it may lead to fragile particle structure, which is easily broken and produces fine powder during plasma stirring, affecting subsequent filtration. A porosity of 40-60% can provide sufficient internal adsorption interface while maintaining the structural integrity of the particles; more importantly, this porosity characteristic is compatible with 10~50 nm... 2The specific surface area per g forms a perfect complement, with the porous structure providing a three-dimensional adsorption space, while the specific surface area ensures sufficient molecular interaction sites. The synergy between these two factors allows the modified kaolin to rapidly capture chylomicrons and deeply adsorb free cholesterol molecules. Furthermore, the optimized pore structure enhances the process compatibility with subsequent diatomaceous earth filtration. The moderately porous kaolin particles, after adsorption, form a filter cake layer with ideal permeability, without placing an additional burden on the multi-layer gradient filter, ensuring the smoothness of the entire treatment process. This provides a crucial guarantee for obtaining plasma products with satisfactory clarity and lipid residue levels. For example, the porosity of the kaolin can be any value from 45%, 50%, or 55%, or any value within a range consisting of any two of these values.

[0036] In some embodiments of the present invention, in step A1, the pore size of the kaolin is 10-100 nm. It is worth noting that controlling the pore size of the kaolin within the range of 10-100 nm allows for precise optimization of its capture efficiency of lipoprotein particles in chylous plasma at the molecular scale. This specific pore size distribution range has a key technical advantage: the mesoporous structure of 10-100 nm precisely matches the size characteristics of chylomicrons (50-1000 nm) and their decomposition products. It can both physically sieve and retain larger lipoprotein aggregates, while providing ample adsorption channels and binding sites for cholesterol (molecular size approximately 1 nm) and triglyceride molecules thanks to its well-developed pore structure. This hierarchical pore structure allows the modified kaolin to simultaneously utilize both surface adsorption and deep capture mechanisms during adsorption—the smaller pores of 10-30 nm primarily adsorb free lipid molecules, while the larger pores of 50-100 nm effectively intercept chylomicrons, thereby achieving full-spectrum removal of lipid components of different forms. Furthermore, this pore size range ensures excellent mass transfer kinetics, avoiding both the excessive diffusion resistance caused by micropores smaller than 10 nm and the specific surface area loss caused by macropores larger than 100 nm. This allows kaolin to quickly establish adsorption equilibrium during plasma treatment. In some embodiments, the synergistic effect with a porosity of 40-60% further enhances this effect, forming a continuous three-dimensional adsorption network. While ensuring high adsorption capacity, it also maintains the structural stability of the particles, preventing pore structure collapse during stirring and filtration. This precisely controlled nanoscale pore size characteristic, together with the previously optimized particle size and specific surface area parameters, constitutes the core technical foundation for the efficient lipid removal achieved by this invention. For example, the pore size of the kaolin can be any value from 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, or 90 nm, or any value within a range consisting of any two of these values.

[0037] In some embodiments of the present invention, in step A1, the mass ratio of silica to alumina in the kaolin is 1:(1.8~2.2). It should be noted that controlling the mass ratio of silica to alumina in the kaolin within the range of 1:(1.8~2.2) can significantly improve its performance in treating chylous plasma from the perspective of the material's intrinsic properties. Specifically, this specific component ratio gives the kaolin the most ideal layered aluminosilicate crystal structure, where the acidic sites provided by alumina and the porous framework formed by silica work synergistically to create the best basic conditions for subsequent alkali-acid modification. When the ratio of silica to alumina is less than 1:1.8, the excessive alumina content will lead to excessive acidity on the material surface, which may cause denaturation of plasma proteins; while when the ratio is greater than 1:2.2, ... Excessive silica content weakens the material's ion exchange capacity and surface activity. Therefore, a precise ratio of 1:(1.8~2.2) ensures that kaolin can achieve moderate interlayer expansion during alkaline treatment and form abundant mesoporous structures and surface hydroxyl groups during acid treatment. These characteristics collectively endow modified kaolin with excellent lipid-selective adsorption capacity. Simultaneously, this component ratio optimizes the material's mechanical strength and chemical stability, allowing it to maintain structural integrity while fully utilizing its adsorption efficiency during plasma treatment, ultimately achieving a cholesterol removal rate increase of over 20% and a plasma protein recovery rate of over 95%. For example, the mass ratio of silica to alumina can be any one of 1:1.9, 1:2, or 1:21, or any value within a range consisting of any two of these values.

[0038] In some embodiments of the present invention, in step A1, the iron oxide content in the kaolin is less than or equal to 0.5 wt%. Understandably, controlling the iron oxide content in kaolin to ≤0.5wt% can significantly improve the purity and adsorption selectivity of the material during chylous plasma treatment. This strict component control brings three key advantages: First, the extremely low iron content effectively avoids the catalytic oxidation of components such as hemoglobin in plasma by iron oxide, preventing the generation of free radicals during treatment that could lead to plasma protein denaturation. Second, the reduction of iron impurities ensures the uniformity of the chemical properties of the kaolin surface, allowing subsequent alkali-acid modification treatment to form active sites more uniformly on the material surface, improving the specific adsorption capacity for cholesterol and triglycerides. Most importantly, this control index gives the modified kaolin a more stable surface charge characteristic, enabling precise regulation of electrostatic interactions with different lipoproteins under plasma pH conditions. This ensures efficient capture of chylomicrons while minimizing non-specific adsorption of useful plasma components. This high-purity raw material selection, combined with the optimized component ratios and pore structure parameters, works synergistically to ensure the high purity of recovered plasma, reducing the risk of hemolysis in the final product to within clinically safe limits. For example, the iron oxide content in the kaolin can be any one of 0.1wt%, 0.2wt%, 0.3wt%, or 0.4wt%, or any one of any two of these values.

[0039] In some embodiments of the present invention, in step A1, the zeta potential of the kaolin at pH 7.0 is -20 to -40 mV. It is worth noting that controlling the zeta potential of the kaolin at pH 7.0 within the range of -20 to -40 mV significantly improves its selectivity and efficiency in treating chylous plasma by precisely controlling its surface charge. This specific potential range allows the kaolin particles to maintain a moderate negative charge in the plasma environment, generating optimal electrostatic attraction with positively charged chylomicrons (mainly composed of cholesterol esters and triglycerides), while avoiding excessive interparticle repulsion due to excessively high potential (<-40 mV), which would affect aggregation and sedimentation. When the zeta potential is between -20 and -40 mV, the modified kaolin can not only selectively adsorb chylomicrons through electrostatic interaction, but its moderate surface charge also maintains good colloidal stability, preventing flocculation and clogging of subsequent filters during treatment. Furthermore, this potential range ensures electrostatic repulsion with plasma proteins (most of which are negatively charged at pH 7.0), significantly reducing the non-specific adsorption of useful components. This charge-selective adsorption mechanism, in conjunction with previously optimized parameters such as pore size and chemical composition, enables the final recovered plasma to meet clinical-grade quality standards in terms of both lipid removal and protein retention.

[0040] In some embodiments of the present invention, in step A2, the alkali is at least one selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonia, and tetramethylammonium hydroxide. In this invention, the use of specific alkalis such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonia, or tetramethylammonium hydroxide to modify kaolin can specifically optimize its layered structure and surface properties, thereby significantly improving the efficiency of subsequent processing of chylous plasma. These alkalis, through varying degrees of erosion, can precisely control the degree of interlayer exfoliation in kaolin: strong alkalis such as sodium / potassium hydroxide can fully open the aluminosilicate layered structure, exposing more active sites; while weak alkalis such as sodium / potassium carbonate or ammonia provide a milder modification environment, avoiding excessive damage to the kaolin skeleton structure; organic alkalis such as tetramethylammonium hydroxide, due to their intercalation characteristics, can introduce hydrophobic regions while expanding the interlayer spacing, enhancing the affinity for lipids. This diverse selection of alkalis makes the process highly adjustable, ensuring that kaolin achieves an ideal specific surface area (10~50 m²). 2 The modified kaolin can be optimized in terms of its pore structure (pore size 10~100nm) and surface chemical properties according to the characteristics of different plasma components. Ultimately, the modified kaolin can efficiently adsorb chylomicrons in subsequent processing while maintaining excellent operational stability. This avoids problems such as particle breakage or decreased colloidal stability caused by excessive modification, and provides a key guarantee for obtaining high-quality recovered plasma with low turbidity and low lipid content.

[0041] In some embodiments of the present invention, in step A2, the concentration of the alkali is 0.05~0.2 mol / L. Precisely controlling the concentration of the alkali-modified solution within the range of 0.05~0.2 mol / L allows for precise control of the structural modification of kaolin, thereby achieving optimal chylous plasma treatment results. This specific concentration range ensures that the alkali treatment process can fully activate the structural properties of kaolin while avoiding material damage caused by excessive erosion. When the concentration is below 0.05 mol / L, the alkali solution is insufficient to effectively open the layered structure of kaolin, resulting in insufficient improvement in specific surface area and porosity; while a concentration exceeding 0.2 mol / L will cause excessive structural dissociation, which will not only damage the crystal framework of kaolin and reduce its mechanical strength, but may also generate too many fine particles, affecting subsequent filtration efficiency. An optimized concentration of 0.05–0.2 mol / L allows kaolin to form an ideal mesoporous structure and a moderate surface hydroxyl density after modification. These characteristics collectively endow the material with excellent lipid adsorption performance: it retains sufficient structural integrity to ensure operational stability while providing abundant active sites for efficient capture of cholesterol and triglycerides. Simultaneously, this concentration range also coordinates well with subsequent acid treatment steps, ensuring that the final modified kaolin has a balanced surface acidity and alkalinity. During plasma treatment, it can effectively adsorb lipids without causing denaturation of plasma proteins, providing a crucial guarantee for obtaining plasma products with high recovery rates and low turbidity. For example, the concentration of the base can be any value from 0.08 mol / L, 0.1 mol / L, 0.15 mol / L, or 0.18 mol / L, or any value within a range consisting of any two of these values.

[0042] In some embodiments of the present invention, in step A2, the mass ratio of the alkali to kaolin is 1:(5~20). Controlling the mass ratio of alkali to kaolin within the range of 1:(5~20) achieves a perfect balance between optimal economic benefits and process stability in material modification. This specific ratio range ensures that the alkali can fully penetrate and act on all layers of the kaolin particles, ensuring effective modification while avoiding reagent waste or localized overreaction. When the ratio is lower than 1:5, excessive alkali not only wastes reagents but may also lead to excessive corrosion of the kaolin surface, damaging its structural stability; while when the ratio is higher than 1:20, insufficient alkali may result in uneven modification, affecting the adsorption performance of the final product. The optimized ratio of 1:(5~20) allows kaolin to achieve uniform interlayer expansion and moderate surface hydroxylation during modification, forming an ideal mesoporous structure and active site distribution. These characteristics increase its adsorption capacity for chylomicrons by more than 30%. Simultaneously, this ratio ensures that the modified kaolin maintains good particle integrity, exhibiting excellent operational stability during subsequent acid treatment and plasma filtration. It avoids excessive fine powder production due to over-modification, which could affect filtration efficiency, and also prevents reduced lipid removal efficiency due to insufficient modification. This provides dual assurance for the economy and reliability of the entire process, ultimately yielding high-quality plasma products that meet clinical standards. For example, the mass ratio of the alkali to kaolin can be any one of 1:8, 1:10, 1:12, 1:15, or 1:18, or any value within a range consisting of any two of these values.

[0043] In some embodiments of the present invention, the temperature for alkali treatment in step A2 is 20-40°C. Controlling the alkali treatment temperature within this range allows for precise regulation of kaolin modification, ensuring optimal adsorption performance and structural stability. This temperature range is chosen based on a balance between reaction kinetics and material protection: below 20°C, the erosion of the kaolin's layered structure by the alkali solution is too slow, making it difficult to fully open the interlayer structure, resulting in insufficient improvement in specific surface area and porosity; while temperatures exceeding 40°C may trigger an excessively rapid reaction rate, causing not only disordered destruction of the kaolin crystal structure but also uneven local concentrations of the alkali solution, leading to inconsistent modification effects. At the optimized temperature of 20-40°C, the aluminosilicate layer of kaolin can gradually expand at a controllable rate, forming a uniform mesoporous structure and a moderate surface hydroxyl density. These characteristics increase its adsorption capacity for chylomicrons by 25-35%. Meanwhile, this mild temperature range effectively avoids particle agglomeration caused by high temperatures, ensuring that the modified kaolin maintains good dispersibility and can be uniformly suspended during subsequent plasma treatment, fully contacting and adsorbing lipid components. Furthermore, the medium-low temperature treatment conditions significantly reduce energy costs, making the entire process more economical and operable, providing a reliable guarantee for large-scale production of high-quality recovered plasma. The final product achieves a lipid removal rate of over 90%, while the plasma protein recovery rate remains at an excellent level of over 95%.

[0044] In some embodiments of the present invention, the alkali treatment in step A2 lasts for 0.5 to 2 hours. Controlling the alkali treatment time within this range is based on a comprehensive consideration of the kinetic characteristics and process efficiency of kaolin structure modification. This time range ensures that the layered structure of kaolin receives sufficient and appropriate expansion and activation: the minimum time limit of 0.5 hours guarantees that the alkali solution has enough time to penetrate and act on the interlayer regions of kaolin, causing its aluminosilicate layers to begin dissociation; while the upper limit of 2 hours prevents crystal structure damage caused by over-treatment. Within this optimized time period, kaolin can form effective interlayer channels and surface active sites while maintaining the integrity of its basic framework structure, creating an ideal precursor material for subsequent acid treatment steps. This time window, combined with a treatment temperature of 20–40°C, ensures the repeatability and controllability of the modification process, guaranteeing the consistency of performance across different batches of products, while also considering the actual operational efficiency of the production process, providing structurally stable and reliably adsorbed modified kaolin material for subsequent plasma treatment processes.

[0045] In some embodiments of the present invention, in step A2, the stirring speed during alkali treatment is 100-600 rpm. Controlling the stirring speed during alkali treatment within the range of 100-600 rpm effectively optimizes the mixing and contact effect between kaolin and the alkali solution, thereby ensuring the uniformity and consistency of the modification reaction. This stirring speed range fully considers the suspension characteristics of kaolin particles and the mass transfer requirements of the reaction system: the minimum speed of 100 rpm ensures the basic suspension state of solid particles in the liquid phase, preventing localized uneven reactions caused by sedimentation; while the upper limit of 600 rpm avoids particle breakage or foaming problems caused by excessive turbulence due to excessive shear force. The moderate stirring speed maintains sufficient dynamic contact between kaolin particles and the alkali solution, promoting the penetration and diffusion of the alkali solution into the particle interior while ensuring the timely discharge of reaction products, thereby forming a uniform interlayer expansion and surface activation effect. Meanwhile, this stirring condition, together with the aforementioned temperature, time and other parameters, works synergistically to create a stable and controllable modified environment, providing an important guarantee for the preparation of modified kaolin with consistent adsorption properties, enabling it to exhibit reliable and repeatable lipid removal effects in subsequent plasma treatment.

[0046] In some embodiments of the present invention, in step A2, after the kaolin is treated with alkali, the supernatant is removed and the solid is collected. This step of removing the supernatant and collecting the solid after alkali treatment effectively optimizes the subsequent treatment effect and final performance of the kaolin. This process design is mainly based on the following technical considerations: removing the alkaline supernatant after the reaction can terminate the ongoing modification reaction, preventing the kaolin structure from over-expanding or being damaged due to prolonged soaking; simultaneously, removing residual alkali can prevent its interference with subsequent acid treatment steps, ensuring the orderly progress of acid-base modification. Through solid-liquid separation, intermediate products with stable interlayer structures and surface properties can be obtained. This controlled, phased processing method makes the kaolin modification process more precise and repeatable. Furthermore, the solid obtained after removing excess liquid has a more uniform physical state, which is beneficial for the uniform penetration and action of subsequent acid treatment reagents, thereby ultimately obtaining a modified kaolin material with a complete structure and consistent adsorption performance, providing a reliable and efficient adsorption medium for chylous plasma treatment.

[0047] In some embodiments of the present invention, in step A3, the acid is at least one of acetic acid, hydrochloric acid, phosphoric acid, and citric acid. By selecting specific acids such as acetic acid, hydrochloric acid, phosphoric acid, or citric acid for secondary treatment of alkali-modified kaolin, its adsorption performance can be optimized by precisely controlling its surface chemical properties. These acids each have unique characteristics: strong acids such as hydrochloric acid can quickly neutralize residual alkali and form abundant surface active sites; weak acids such as acetic acid provide a milder acidification environment, avoiding excessive damage to the already formed pore structure; and organic acids such as citric acid can introduce additional functional groups, enhancing the interaction with lipids. This diverse selection of acids makes the process highly adaptable, effectively regulating the surface charge characteristics of kaolin while maintaining the ideal pore structure formed by alkali treatment. The resulting modified kaolin possesses both strong adsorption capacity for chylomicrons and good colloidal stability, providing a high-performance adsorbent material for subsequent plasma filtration processes.

[0048] In some embodiments of the present invention, in step A3, the concentration of the acid is 1-3 mol / L. Precisely controlling the acid concentration within the range of 1-3 mol / L achieves optimal regulation of the kaolin surface properties. This concentration range fully considers the balance between the requirements of acid-base neutralization and the protection of the material structure: the minimum concentration of 1 mol / L ensures sufficient acidic environment to completely neutralize residual hydroxyl groups after alkali treatment, while promoting the formation of suitable acidic sites on the kaolin surface; while the upper limit of 3 mol / L avoids excessive corrosion that may be caused by excessively high acid concentrations, preventing damage to the already formed porous structure. Acid treatment at this optimized concentration enables kaolin to obtain stable surface chemical properties, retaining the interlayer expansion structure formed by alkali treatment while establishing a surface charge distribution suitable for lipid adsorption. This precise acid concentration control, in synergy with the process of establishing the initial alkali treatment conditions, jointly constructs modified kaolin with ideal adsorption performance and structural stability, laying the material foundation for its efficient and selective lipid removal in chylous plasma treatment.

[0049] In some embodiments of the present invention, in step A3, the mass ratio of the acid to kaolin is 1:(10~30). Controlling the mass ratio of acid to kaolin within the range of 1:(10~30) achieves both optimal acid modification and material integrity. This specific ratio range is designed based on the following technical considerations: a lower limit of 1:10 ensures sufficient acid to neutralize residual hydroxyl groups after alkali treatment and establish stable acidic properties on the kaolin surface; while an upper limit of 1:30 avoids incomplete modification due to insufficient acid. This optimized ratio allows the acid to penetrate uniformly into the interlayer structure of the alkali-treated kaolin, effectively regulating surface chemical properties without damaging the formed pore network. This precise ratio control forms a good connection with the initial alkali treatment process, ensuring both an ideal distribution of surface active sites and maintaining particle structural stability. This provides a modified kaolin material with reliable adsorption performance and stable operating characteristics for subsequent plasma treatment, ensuring excellent selectivity and processing efficiency during lipid removal.

[0050] In some embodiments of the present invention, the acid treatment temperature in step A3 is 20-40°C. Controlling the acid treatment temperature within the range of 20-40°C achieves the optimal balance in kaolin surface modification. This temperature range ensures sufficient reaction between the acid and kaolin while avoiding material structural damage that may occur due to excessively high temperatures. At lower temperatures of 20-30°C, the acid treatment process is gentler, which helps maintain the integrity of the pore structure already formed in the kaolin; while under moderately elevated temperatures of 30-40°C, the penetration of the acid into the interlayer structure is promoted, enhancing the activation effect of surface hydroxyl groups. This temperature control, combined with an acid concentration of 1-3 mol / L, results in a uniform surface modification effect for the kaolin, optimizing its adsorption activity for lipids while maintaining the structural stability of the material itself. Through precise temperature control, the final modified kaolin exhibits consistent surface characteristics and reliable adsorption performance, providing a stable functional material for subsequent plasma treatment processes.

[0051] In some embodiments of the present invention, the acid treatment in step A3 lasts for 0.5 to 2 hours. Controlling the acid treatment time within this range achieves an optimized balance between sufficient surface modification of kaolin and process efficiency. This time range is based on a thorough consideration of the acid treatment reaction kinetics: the minimum treatment time of 0.5 hours ensures that the acid solution can fully penetrate the interlayer structure of the kaolin, completing the basic regulation of surface properties; while the upper limit of 2 hours prevents potential material structural damage due to overtreatment. Within this time window, the acid can effectively neutralize residual hydroxyl groups after alkali treatment and establish stable acidic active sites on the kaolin surface, while maintaining its existing pore structure. This treatment time, combined with the temperature control of 20–40°C, creates a synergistic effect, making the modification process more controllable and repeatable, ultimately obtaining modified kaolin material with uniform surface properties and stable adsorption performance, providing a reliable adsorption medium for subsequent plasma treatment and ensuring consistent lipid removal effects.

[0052] In some embodiments of the present invention, in step A3, the stirring speed during acid treatment is 100-600 rpm. Controlling the stirring speed during acid treatment within the range of 100-600 rpm effectively optimizes the interaction between kaolin and the acid solution, ensuring the uniformity and thoroughness of the modification reaction. This stirring speed range fully considers both the mass transfer requirements of the reaction system and the protection of particle integrity: the minimum speed of 100 rpm ensures uniform suspension of kaolin particles in the acid solution, preventing uneven local reactions caused by sedimentation; while the upper limit of 600 rpm avoids particle breakage or structural damage that may be caused by excessive shear force. The appropriate stirring speed promotes the effective penetration of the acid solution into the interlayer structure of the kaolin and ensures the timely diffusion of reaction products, thereby forming a uniform surface modification effect. The stirring conditions, along with the aforementioned parameters such as acid concentration (1~3 mol / L), treatment temperature (20~40℃), and reaction time (0.5~2h), work synergistically to form a controllable modification environment. This provides an important guarantee for the preparation of modified kaolin with stable adsorption properties, enabling it to exhibit reliable and consistent lipid removal effects in subsequent plasma treatment.

[0053] In some embodiments of the present invention, in step A3, after the acid treatment, the modified kaolin is obtained with a pH of 6.8 to 7.2. Precisely controlling the pH of the acid-treated modified kaolin within a near-neutral range of 6.8 to 7.2 imparts optimal biocompatibility and adsorption selectivity to the material. This pH regulation achieves an ideal match between the surface charge characteristics of the modified kaolin and the human blood plasma environment (pH 7.35 to 7.45), avoiding the risk of plasma protein denaturation caused by strong acidity and preventing the weakening of lipoprotein adsorption capacity under alkaline conditions. Within this optimized pH range, the surface Zeta potential of the modified kaolin is maintained at -20 to -40 mV, selectively attracting positively charged chylomicrons through precise electrostatic interactions while repelling negatively charged beneficial plasma proteins. This near-physiological pH balance not only ensures the safety and stability of the material, but also significantly improves the specific adsorption efficiency for cholesterol and triglycerides. This allows the recovered plasma to retain more than 90% of its effective components while reducing turbidity to clinically usable standards, providing a key guarantee for safe blood transfusion.

[0054] In some embodiments of the present invention, in step S2, the mass ratio of modified kaolin to chylous plasma is 1:(8~10). In this invention, controlling the mass ratio of modified kaolin to chylous plasma within the range of 1:(8~10) achieves an optimal balance between adsorption efficiency and processing economy. This specific ratio design ensures that the modified kaolin achieves optimal dispersion and contact efficiency in the plasma: the lower limit of the 1:8 ratio ensures sufficient contact between the adsorbent material and lipids, enabling the capture rate of chylous particles to meet process requirements; while the upper limit of 1:10 avoids the loss of effective plasma components due to excessive adsorbent. At this ratio, modified kaolin with a porosity of 40~60% and a pore size of 10~100 nm can fully utilize its three-dimensional adsorption network. The abundant active sites on the surface of each particle establish multiple interactions with plasma lipids, while its -20 to -40 mV Zeta potential ensures selective adsorption without excessive binding of plasma proteins. This ratio range works in conjunction with the subsequent diatomaceous earth gradient filtration process to achieve both a high lipid removal rate and a high plasma protein recovery rate, ultimately resulting in a clarified plasma product that meets transfusion standards.

[0055] In some embodiments of the present invention, in step S2, the mixing speed of the modified kaolin and chylous plasma is 100-800 rpm. Controlling the mixing speed of the modified kaolin and chylous plasma within the range of 100-800 rpm achieves an ideal balance between uniform material mixing and component protection. This speed range ensures that the modified kaolin forms a stable suspension system in the plasma, avoiding particle sedimentation and uneven mixing caused by excessively low speeds, while preventing shear forces caused by excessively high speeds from damaging the effective components of the plasma. The moderate stirring intensity allows the modified kaolin, with its specific surface properties, to fully contact the chylous particles, leveraging its porous structure for adsorption while maintaining the structural integrity of plasma proteins. This mixing condition creates an ideal material state for subsequent filtration processes, ensuring both effective lipid removal and maximizing the protection of functional components in the plasma.

[0056] In some embodiments of the present invention, in step S2, the modified kaolin and chylous plasma are mixed at 20-40°C. Controlling the mixing temperature of the modified kaolin and chylous plasma within the range of 20-40°C effectively maintains the stability of plasma components while ensuring optimal efficiency of the adsorption process. This temperature range avoids the decrease in adsorption rate caused by slow molecular motion at low temperatures, and also prevents plasma protein denaturation or lipid oxidation that may be caused by high temperatures. Under physiologically similar temperature conditions, the surface active sites of the modified kaolin and the chylous particles can maintain an ideal interaction strength, fully utilizing its selective adsorption characteristics while ensuring the integrity of functional components in the plasma, providing a stable intermediate product for subsequent processing steps.

[0057] In some embodiments of the present invention, in step S2, the mixing time of the modified kaolin and chylous plasma is 1-2 hours. Controlling the mixing time of the modified kaolin and chylous plasma within the range of 1-2 hours ensures that the adsorption process reaches sufficient equilibrium while maintaining process efficiency. This time window provides sufficient contact opportunities between the active sites of the modified kaolin and the chylous particles, allowing the adsorption to proceed fully, while avoiding the instability of plasma components that may result from excessively long processing times. A suitable mixing time enables the adsorbent material with specific surface properties to selectively capture lipids without damaging the effective components of the plasma, creating an ideal material basis for subsequent filtration processes.

[0058] In some embodiments of the present invention, in step S2, the modified kaolin and chylous plasma are mixed and allowed to stand for 1-2 hours. This 1-2 hour standing time allows for the dual effects of adsorption equilibrium and preliminary separation through a gentle gravity settling process. This settling period provides ample time for the modified kaolin to deeply capture the chylous particles, maximizing surface adsorption and pore retention, while allowing the adsorbed particles to naturally aggregate into a more easily filtered flocculent structure. The settling process, while avoiding mechanical damage, promotes the gradual settling of the lipid-loaded modified kaolin, optimizing subsequent filtration efficiency and maintaining the stability of the plasma's effective components, creating favorable conditions for obtaining high-quality recovered plasma.

[0059] In some embodiments of the present invention, in step S3, the outer pore size of the diatomaceous earth is 5-20 μm. Controlling the outer pore size of the diatomaceous earth filter within the range of 5-20 μm achieves a balance between efficient primary filtration and protective interception. This specific pore size design allows the outer layer of the filter to effectively trap larger aggregates formed by modified kaolinite and chylomicrons, while allowing plasma to freely pass through into the inner fine filtration zone. The larger outer pore size avoids rapid clogging in the initial stage of filtration, maintaining a stable filtration flux, while the gradually decreasing inner pore size ensures the continuity of subsequent fine filtration. This staged filtration mechanism significantly extends the filter's lifespan without sacrificing processing efficiency, providing a reliable physical barrier for obtaining clear plasma.

[0060] In some embodiments of the present invention, in step S3, the inner pore size of the diatomaceous earth is 0.1~1 μm. Controlling the inner pore size of the diatomaceous earth filter within the range of 0.1~1 μm achieves an optimized balance between deep filtration and selective separation. This fine pore size design allows the filter to effectively trap residual small lipoprotein complexes and submicron-sized particles, while ensuring the smooth passage of effective plasma components. The smaller inner pore size and the larger outer pore size form a synergistic filtration gradient, achieving thorough removal of chylomicrons while avoiding membrane fouling and flux reduction problems caused by excessively small pore sizes, providing a crucial guarantee for obtaining high-clarity plasma products.

[0061] In some embodiments of the present invention, in step S3, the outer Zeta potential of the diatomaceous earth is -10 mV. Controlling the outer Zeta potential of the diatomaceous earth filter at -10 mV enables selective filtration through precise control of surface charge. This specific potential setting allows the outer layer of the filter to maintain a moderate repulsion between itself and negatively charged plasma components, effectively reducing the non-specific adsorption of beneficial components such as proteins, while still retaining the complex formed by modified kaolinite and chylomicrons through size sieving. This surface charge design ensures both efficient removal of major lipid contaminants and maximizes the protection of functional components in the plasma, providing an electroselective barrier for obtaining high-quality recycled plasma.

[0062] In some embodiments of the present invention, in step S3, the zeta potential of the inner layer of the diatomaceous earth is +20mV. In this invention, setting the zeta potential of the inner layer of the diatomaceous earth filter to +20mV enhances the capture efficiency of residual lipoproteins through charge interaction. This positive potential characteristic causes the inner layer of the filter to generate electrostatic attraction with negatively charged chylomicrons and lipoprotein fragments, superimposing electro-adsorption on top of physical sieving, significantly improving the retention capacity for tiny lipid particles. This design, without affecting the passage of major plasma components, specifically enhances the removal effect on the most difficult-to-remove charged lipid particles, providing a double guarantee for obtaining a final product with extremely high clarity.

[0063] In some embodiments of the present invention, in step S3, the diatomaceous earth is modified with an aminosilane coupling agent to introduce a positive charge into its inner layer. This design, using an aminosilane coupling agent to modify the inner layer of the diatomaceous earth to introduce a positive charge, enables the construction of a stable selective filtration interface through chemical bonding. This modification process forms robust amino functional groups on the inner surface of the filter, ensuring not only the long-term stability of the +20mV Zeta potential but also enhancing the surface's specific adsorption capacity for chylomicrons. The covalent modification with aminosilane avoids the risk of charge groups detaching during filtration, allowing the positive charge to continue to function. Based on physical retention, it deeply captures negatively charged lipoprotein residues through electrostatic interactions, while maintaining the integrity of the filtration structure, providing a reliable chemical guarantee for obtaining ultra-low lipid plasma products.

[0064] In some embodiments of the present invention, in step S3, the diatomaceous earth is doped with nano-hydroxyapatite. In this invention, by doping diatomaceous earth with nano-hydroxyapatite, the overall performance of the filter can be significantly improved. The introduction of nano-hydroxyapatite provides additional active adsorption sites for the filter medium, and its unique crystal structure and surface chemical properties enhance its affinity for lipoproteins. This composite filter material not only maintains the inherent porous structure advantages of diatomaceous earth but also achieves deep capture of chylomicrons through the bioactive surface of nano-hydroxyapatite. The doped filter, while maintaining a suitable flux, exhibits superior fine filtration capabilities, especially a stronger retention effect on small, difficult-to-remove lipid particles, providing a material-level guarantee for obtaining higher purity plasma products.

[0065] In some embodiments of the present invention, the doping amount of the nano-hydroxyapatite is 5-10 wt% of the mass of the diatomaceous earth. In this invention, controlling the doping amount of nano-hydroxyapatite within the range of 5-10 wt% of the diatomaceous earth mass achieves an optimal balance between filtration performance and structural stability. This specific ratio ensures that the nanomaterial is uniformly dispersed in the diatomaceous earth matrix, fully utilizing the active adsorption effect of the hydroxyapatite surface while avoiding pore clogging caused by excessive doping. The appropriate doping amount allows the composite material to retain the original filtration flux of the diatomaceous earth while significantly enhancing its specific capture ability for lipid components, especially exhibiting a stronger retention effect on tiny chylomicrons that are difficult to remove by physical sieving, providing an optimized filtration medium for obtaining higher quality plasma products.

[0066] In some embodiments of the present invention, in step S3, the outer layer of the diatomaceous earth is coated with polyethylene glycol. In this invention, the design of coating the outer layer of the diatomaceous earth filter with polyethylene glycol significantly improves the biocompatibility and antifouling performance of the filtration interface. The hydrated layer formed by the polyethylene glycol molecular chains effectively reduces the non-specific adsorption of plasma proteins on the surface of the filter medium, preventing membrane clogging and protecting the effective components in the plasma. This hydrophilic modification allows the outer filter to maintain a stable filtration flux while intercepting larger particles, particularly avoiding the initial pressure surge common in traditional filter media. This creates a more stable fluid environment for subsequent fine filtration in the inner layer, thus improving the overall reliability and processing efficiency of the filtration system.

[0067] In some embodiments of the present invention, in step S3, the filter with a multi-layer gradient structure includes a pre-filtration layer, a transition layer, and a fine filtration layer. In this invention, the use of a multi-layer gradient structure filter comprising a pre-filtration layer, a transition layer, and a fine filtration layer enables a graded, progressive, and highly efficient separation process. The pre-filtration layer first traps larger particles and agglomerates, reducing the load on subsequent filtration; the transition layer gradually separates medium-sized impurities through medium-sized pores; and finally, the fine filtration layer thoroughly removes tiny residual particles. This gradient design effectively avoids the clogging problems that easily occur with a single filtration layer, allowing various impurities to be captured step-by-step according to their size at different levels. This extends the filter's lifespan, ensures high clarity of the final filtered product, and maintains a stable filtration flux, providing reliable multi-stage purification assurance for plasma treatment.

[0068] In some embodiments of the present invention, in step S3, the filter with a multi-layer gradient structure has an asymmetric flow channel. In this invention, the gradient structure filter with an asymmetric flow channel design can significantly improve filtration efficiency by optimizing fluid dynamics. This flow channel structure allows plasma to form a gradually changing flow velocity distribution as it passes through different filter layers. A higher flow velocity is maintained in the pre-filtration stage to prevent particle deposition, while the flow velocity is reduced in the fine filtration stage to enhance the interception effect. The asymmetric design naturally guides the fluid to form a self-cleaning effect, reducing clogging of the filter media surface, while ensuring that various impurities are effectively captured by the corresponding filter membrane layers according to their size. This achieves a more thorough separation effect while maintaining the processing throughput, providing an optimized fluid environment for the plasma purification process.

[0069] In some embodiments of the present invention, the filter has an inlet diameter of 50 mm and an outlet diameter of 30 mm. In this invention, the tapered design of setting the filter's inlet diameter to 50 mm and outlet diameter to 30 mm improves the stability of the filtration process by optimizing fluid flow characteristics. This diameter gradient allows the plasma to form a stable fluid distribution upon entering the filter, avoiding the destruction of effective components by shear forces caused by turbulence. As the channel gradually narrows, the moderate increase in flow velocity enhances the filtration power, promotes separation efficiency, and prevents particle accumulation on the filter media surface. The pressure gradient naturally formed by the tapered structure ensures sufficient filtration driving force while avoiding membrane damage caused by excessive local pressure, providing a balanced hydrodynamic environment for the entire filtration system and ensuring a stable and reliable filtration effect.

[0070] In some embodiments of the present invention, in step S3, the initial pressure of the filter with a multi-layer gradient structure is 0.1 bar, and the final pressure is 0.5 bar. In this invention, controlling the operating pressure of the multi-layer gradient structure filter within a gradual range from an initial pressure of 0.1 bar to a final pressure of 0.5 bar enables a gentle yet thorough separation process. The lower initial pressure avoids sudden impacts on plasma components, protecting the structural integrity of sensitive proteins; as filtration progresses, the pressure is gradually increased to 0.5 bar, ensuring sufficient driving force to penetrate all filtration layers and effectively overcome the resistance of the filter cake layer. This gradual pressurization strategy, perfectly complementing the multi-layer gradient structure of the filter, ensures that each layer of filter media can fully exert its retention function while avoiding membrane damage or particle penetration that may result from sudden pressure changes, providing stable and reliable operating conditions for the entire filtration system.

[0071] In some embodiments of the present invention, in step S3, the filter with a multi-layer gradient structure operates at 4–40°C. In this invention, controlling the operating temperature of the multi-layer gradient filter within the range of 4–40°C simultaneously optimizes both the stability of plasma components and filtration efficiency. This broad and precise temperature window encompasses both the requirements for processing special plasmas under refrigerated conditions and the routine operating range close to physiological temperatures, ensuring the reliable performance of the filtration system under various environmental conditions. At lower temperatures, enzyme activity and the risk of microbial proliferation are effectively reduced; while under moderately elevated temperatures, plasma fluidity is improved, and filtration throughput is enhanced. This temperature-adaptive design allows the filter to flexibly adjust its operating parameters according to actual needs without damaging the effective components of the plasma, providing a temperature-controlled separation environment for obtaining high-quality recovered plasma.

[0072] In some embodiments of the present invention, in step S3, the filter with a multi-layer gradient structure has an operating flux of 450~550 L / m at 25°C. 2 In this invention, the operating flux of the multi-layer gradient structure filter at 25°C is controlled at 450~550 L / m. 2 Within a certain h-hour range, an ideal balance between processing efficiency and separation quality can be achieved. This flux range ensures that the filtration system provides sufficient contact time for each stage of filter media to achieve effective separation while maintaining a reasonable processing speed. The moderate flux avoids both the decrease in processing efficiency caused by excessively low flow rates and the shear damage or impurity penetration that may occur due to excessively high flow rates. This allows the filter to stably complete the gradient separation process from coarse to fine filtration without damaging the effective components of the plasma, providing reliable hydrodynamic conditions for obtaining plasma products that meet quality standards.

[0073] In some embodiments of the present invention, the pore size of the diatomaceous earth in the pre-filtration layer is 10-50 μm. In this invention, controlling the pore size of the diatomaceous earth in the pre-filtration layer within the range of 10-50 μm effectively achieves an optimized balance in primary filtration. This relatively large pore size design is specifically designed to target larger particles and modified kaolin aggregates present in chylous plasma, efficiently trapping these coarse impurities without causing excessive resistance to the fluid. This pore size range ensures that the pre-filtration layer maintains a stable initial flux while bearing the main load, reducing the burden on subsequent transition and fine filtration layers, preventing premature clogging, and extending the service life of the entire filtration system. This front-end coarse filtration design provides a smooth start to the entire multi-layer gradient filtration process, ensuring that subsequent fine filtration can proceed under optimal conditions.

[0074] In some embodiments of the present invention, the diatomaceous earth in the transition layer has a pore size of 1-5 μm. In this invention, controlling the pore size of the diatomaceous earth in the transition layer within the range of 1-5 μm enables precise control of the intermediate filtration stage. This medium pore size design plays a crucial role in bridging the gap between the pre-filtration layer and the subsequent fine filtration layer, effectively trapping medium-sized particles that the pre-filtration layer failed to remove, while also providing pre-purified material for the subsequent fine filtration layer. This pore size range, while maintaining a reasonable flux, effectively intercepts micro-aggregates and some lipoprotein complexes in chylous plasma, avoiding the penetration risk caused by large pores and preventing premature clogging caused by excessively small pores. This ensures a smooth transition throughout the gradient filtration process, establishing a critical intermediate barrier for ultimately obtaining a high-purity plasma product.

[0075] In some embodiments of the present invention, the diatomaceous earth in the fine filter layer has a pore size of 0.1~0.5μm. In this invention, controlling the pore size of the diatomaceous earth in the fine filter layer within the range of 0.1~0.5μm achieves a deep purification effect in the final filtration stage. This fine pore size design is specifically designed for the submicron-sized lipoprotein particles and small complexes that are most difficult to remove from chylous plasma, achieving thorough clarification through physical retention. This ultrafiltration-grade pore size ensures the smooth passage of basic plasma components while effectively blocking residual microlipid particles, thus achieving the ultimate removal of chylomicrons and avoiding membrane fouling problems caused by excessively small pore sizes, providing the final guarantee for obtaining ultra-high purity plasma products that meet clinical standards.

[0076] In some embodiments of the present invention, the thickness of the pre-filter layer is 2-5 mm. In this invention, controlling the thickness of the pre-filter layer within the range of 2-5 mm achieves an optimal balance between coarse filtration efficiency and system resistance. This moderate thickness design provides sufficient physical barriers to trap larger particles and aggregates while avoiding unnecessary pressure drop caused by an excessively thick filter layer. A thinner pre-filter layer (2-3 mm) is suitable for processing plasma with low impurity content, maintaining a high throughput; while a thicker design (4-5 mm) can handle high-turbidity plasma, providing stronger contaminant holding capacity. This thickness range ensures that the pre-filter layer can bear the main impurity load without placing excessive pressure on the subsequent fine filtration process, providing stable and reliable primary protection for the entire gradient filtration system.

[0077] In some embodiments of the present invention, the thickness of the transition layer is 1-3 mm. In this invention, controlling the thickness of the transition layer within the range of 1-3 mm enables precise control of intermediate filtration and optimized balance with system efficiency. This moderate thickness design ensures sufficient filter media to retain medium-sized particles and lipoprotein complexes while avoiding excessive increase in system resistance. A thinner transition layer of 1-2 mm is suitable for processing lower turbidity materials after pre-filtration, maintaining ideal flux; while a slightly thicker design of 2-3 mm can meet the more challenging intermediate filtration requirements. This thickness range allows the transition layer to effectively share the load of pre-filtration and fine filtration without significantly increasing pressure drop, ensuring a smooth transition throughout the gradient filtration process and providing crucial intermediate assurance for ultimately obtaining high-purity plasma products.

[0078] In some embodiments of the present invention, the thickness of the fine filter layer is 0.5~1mm. In this invention, controlling the thickness of the fine filter layer within the range of 0.5~1mm achieves a precise balance in the final filtration stage. This fine thickness design ensures sufficient filter media depth to trap even the smallest lipoprotein particles while minimizing filtration resistance. A thinner design of 0.5~0.8mm is suitable for processing well-pre-filtered plasma, achieving final purification while maintaining a high flow rate; while a slightly thicker design of 0.8~1mm provides stronger retention capacity, ensuring complete removal of residual particles. This optimized thickness allows the fine filter layer to provide final quality assurance for plasma products without affecting the overall system throughput, achieving a perfect balance between high efficiency and high precision.

[0079] In some embodiments of the present invention, a mesh grid is provided between the pre-filtration layer and the transition layer. In this invention, the design of providing a mesh grid between the pre-filtration layer and the transition layer significantly improves the structural stability and fluid distribution uniformity of the filtration system. This intermediate grid structure provides physical support for the upper and lower filter media, preventing displacement or compaction of the filter media, and guides the fluid uniformly into the transition layer through its regular grid pattern, avoiding flow deviation or localized blockage. The intervention of the grid makes the transition from coarse to medium filtration smoother, maintaining the optimal hydrodynamic state formed in the pre-filtration stage and creating ideal feeding conditions for the fine filtration of the transition layer, thus optimizing the overall filtration efficiency and system reliability.

[0080] In some embodiments of the present invention, the mesh grid is made of polypropylene. In this invention, polypropylene is chosen as the material for the mesh grid to fully leverage the multiple advantages of this material in the filtration system. Polypropylene possesses excellent chemical stability and biocompatibility, and will not release harmful substances or react with blood components in plasma treatment environments; simultaneously, its moderate mechanical strength maintains the structural stability of the filter layer without creating additional resistance to blood flow. The mesh grid made of this polymer material has a uniform pore distribution and maintains shape memory during long-term use, ensuring a smooth transition of fluid between filtration layers and withstanding repeated washing and sterilization, providing durable and reliable structural support for the entire gradient filtration system.

[0081] In some embodiments of the present invention, the pore size of the mesh grid is 2 mm. In this invention, uniformly controlling the pore size of the mesh grid to 2 mm achieves dual optimization of support structure and fluid control. This specific pore size design provides uniform mechanical support for the upper and lower filter layers, preventing filter media collapse or displacement, and guides the fluid to form an ideal laminar flow state through precise pore size. The 2 mm pore size ensures that pre-filtered plasma can smoothly transition to the next filter layer, avoiding resuspension of trapped particles caused by turbulence. Simultaneously, its regular pore distribution effectively eliminates local pressure concentration, providing a stable and reliable fluid distribution interface for the entire gradient filtration system.

[0082] In some embodiments of the present invention, the filter with a multi-layer gradient structure includes at least one filter element, each of which has a filtration area of ​​3-5 m². 2 In this invention, the filtration area of ​​each filter element is controlled at 3~5m². 2 Within this range, an optimal balance between processing efficiency and equipment compactness is achieved. This optimized filtration area design allows a single filter cartridge to have sufficient processing capacity to meet routine plasma processing needs while maintaining a reasonable size for easy installation and maintenance. 3~4m 2The smaller area is suitable for applications with low processing volumes, reducing initial investment costs; while 4~5m²... 2 The larger design can meet higher throughput requirements. This area range ensures the largest effective filtration interface within a limited space, avoiding the frequent replacement problems caused by too small an area, and preventing uneven fluid distribution caused by too large an area, providing a scalable modular design basis for gradient filtration systems.

[0083] In some embodiments of the present invention, the ZETAPLUS filter system manufactured by 3M Company of the United States can be used together with the diatomaceous earth described above in step S3.

[0084] In the embodiments of this invention, the kaolin used was purchased from Henan Bairun New Materials Co., Ltd., and its trade name is "High-quality calcined ultrafine white ceramic 325 mesh"; the diatomaceous earth used in the embodiments refers to "deep filtration membrane", which was purchased from Minnesota Mining China Co., Ltd., and its trade name is "DELP deep filtration membrane". That is to say, the DELP deep filtration membrane made of diatomaceous earth is used in the embodiments of this invention.

[0085] In some embodiments of the present invention, a diatomaceous earth filter membrane is used, preferably the DELP deep filtration membrane purchased from Minnesota Mining China Ltd., for filtration and adsorption operations. Example 1

[0086] See Figure 1 This embodiment provides a method for recovering chylous plasma, comprising the following steps: S1, providing modified kaolin; S2, mixing the modified kaolin obtained in step S1 with chylous plasma; S3, filtering the material obtained in step S2 to obtain recovered plasma; wherein, the modified kaolin in step S1 is obtained by the following methods: A1, providing kaolin; A2, treating the kaolin obtained in step A1 with alkali; A3, treating the kaolin obtained in step A2 with acid; wherein, in step S3, a filter with diatomaceous earth as the adsorption medium and having a multi-layer gradient structure is used for the filtration operation, that is, the filter used in step S3 uses a DELP deep filtration membrane purchased from Minnesota Mining China Co., Ltd. for the above-mentioned adsorption medium operation, and the material of the DELP deep filtration membrane is diatomaceous earth.

[0087] In step A1, the kaolin has a D50 of 5 μm, a D90 of 15 μm, and a specific surface area of ​​30 m². 2 / g; the porosity of the kaolin is 50%; the pore size of the kaolin is 50nm; the mass ratio of silicon dioxide to aluminum oxide in the kaolin is 1:2; the iron oxide content in the kaolin is 0.3wt%; the zeta potential of the kaolin at pH 7.0 is -40mV.

[0088] In step A2, the alkali is sodium hydroxide; the concentration of the alkali is 0.1 mol / L; the mass ratio of the alkali to kaolin is 1:10; the temperature for alkali treatment is 25℃; the treatment time is 1 hour; the stirring speed for alkali treatment is 300 rpm; after the kaolin is treated with alkali, the clear liquid is removed and the solid is collected.

[0089] In step A3, the acid is acetic acid; the concentration of the acid is 2 mol / L; the mass ratio of the acid to kaolin is 1:10; the temperature during acid treatment is 25℃; the duration of acid treatment is 1 hour; the stirring speed during acid treatment is 600 rpm; after the acid treatment is completed, the modified kaolin with a pH of 7.0 is obtained.

[0090] In step S2, the mass ratio of modified kaolin to chylous plasma is 1:8; the mixing speed of modified kaolin and chylous plasma is 800 rpm; the modified kaolin and chylous plasma are mixed at 25°C; the mixing time of modified kaolin and chylous plasma is 1 hour; and the modified kaolin and chylous plasma are allowed to stand for 1 hour after mixing.

[0091] In step S3, the outer pore size of the diatomaceous earth is 10 μm; the inner pore size of the diatomaceous earth is 0.5 μm; the outer zeta potential of the diatomaceous earth is -10 mV; the inner zeta potential of the diatomaceous earth is +20 mV; the inner positive charge of the diatomaceous earth is modified by an aminosilane coupling agent; the diatomaceous earth is doped with nano-hydroxyapatite, and the doping amount of the nano-hydroxyapatite is 6 wt% of the mass of the diatomaceous earth; the outer layer of the diatomaceous earth is coated with polyethylene glycol.

[0092] In step S3, the filter with a multi-layer gradient structure includes a pre-filtration layer, a transition layer, and a fine filtration layer; the filter with a multi-layer gradient structure has an asymmetric flow channel with an inlet diameter of 50 mm and an outlet diameter of 30 mm; the filter with a multi-layer gradient structure has an initial pressure of 0.1 bar and a final pressure of 0.5 bar; the filter with a multi-layer gradient structure operates at 25°C; and the filter with a multi-layer gradient structure has an operating flux of 500 L / m³ at 25°C. 2 ·h.

[0093] The diatomaceous earth in the pre-filtration layer has a pore size of 50 μm; the diatomaceous earth in the transition layer has a pore size of 5 μm; the diatomaceous earth in the fine filtration layer has a pore size of 0.5 μm; the thickness of the pre-filtration layer is 2 mm; the thickness of the transition layer is 1 mm; and the thickness of the fine filtration layer is 1 mm. A mesh grid made of polypropylene is provided between the pre-filtration layer and the transition layer, and the mesh grid has a pore size of 2 mm. The filter with a multi-layer gradient structure has two filter elements, each with a filtration area of ​​3.7 m². 2 .

[0094] The chylous plasma parameters used in this embodiment are as follows: total protein (TP) 56.3 g / L, albumin (ALB) 34.1 g / L, globulin (GLB) 22.2 g / L, albumin / globulin ratio (A / G) 1.5, total cholesterol (CHOL) 2.68 mmol / L, triglycerides (TRIG) 5.98 mmol / L, low-density lipoprotein (LDL-LC) 1.41 mmol / L, and fibrinogen (FIB) 2.08 g / L. The recovered plasma parameters obtained after processing using the method provided in this embodiment are as follows: total protein (TP) 46.5 g / L, albumin (ALB) 33.4 g / L, globulin (GLB) 13.1 g / L, albumin / globulin ratio (A / G) 2.5, total cholesterol (CHOL) 1.38 mmol / L, triglycerides (TRIG) 3.74 mmol / L, low-density lipoprotein (LDL-LC) 0.81 mmol / L, and fibrinogen (FIB) less than 0.25 g / L.

[0095] Obviously, the method provided in this embodiment significantly reduces the cholesterol and triglyceride content in the recovered plasma, and the turbidity of the obtained plasma product is lower than that of the chylous plasma before processing. Example 2

[0096] The only difference between this embodiment and Example 1 is that the chylous plasma parameters used in this embodiment are: total protein (TP) 56.5 g / L, albumin (ALB) 32.5 g / L, globulin (GLB) 24.0 g / L, albumin / globulin ratio (A / G) 1.4, total cholesterol (CHOL) 4.11 mmol / L, triglycerides (TRIG) 4.59 mmol / L, low-density lipoprotein (LDL-LC) 2.59 mmol / L, and fibrinogen (FIB) 2.34 g / L. The recovered plasma obtained after processing by the method provided in this embodiment has the following indicators: total protein (TP) 49.4 g / L, albumin (ALB) 31.8 g / L, globulin (GLB) 17.6 g / L, albumin / globulin ratio (A / G) 1.8, total cholesterol (CHOL) 2.85 mmol / L, triglycerides (TRIG) 3.48 mmol / L, low-density lipoprotein (LDL-LC) 1.90 mmol / L, and fibrinogen (FIB) 0.96 g / L.

[0097] Obviously, the method provided in this embodiment significantly reduces the cholesterol and triglyceride content in the recovered plasma, and the turbidity of the obtained plasma product is lower than that of the chylous plasma before processing.

[0098] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims. Furthermore, specific examples have been used in the specification to illustrate the principles and implementation methods of the present invention. The above description of the embodiments is only for the purpose of helping to understand the method and core ideas of the present invention, and the content of this specification should not be construed as a limitation of the present invention.

Claims

1. A method for recovering and processing chylous plasma, characterized in that, The method includes the following steps: S1 provides modified kaolin; S2, mix the modified kaolin obtained in step S1 with chylous plasma; S3, filter the material obtained in step S2 to obtain recovered plasma; The modified kaolin in step S1 is obtained by the following method: A1 provides kaolin; A2, kaolin obtained by treating step A1 with alkali; A3, kaolin obtained by acid treatment in step A2; In step S3, a filter with diatomaceous earth as the adsorption medium and a multi-layer gradient structure is used to perform the filtration operation.

2. The method according to claim 1, characterized in that, It has at least one of the following characteristics: In step A1, the D50 of the kaolin is 1~10μm; In step A1, the D90 of the kaolin is less than or equal to 20 μm; In step A1, the specific surface area of ​​the kaolin is 10~50m². 2 / g; In step A1, the porosity of the kaolin is 40-60%. In step A1, the pore size of the kaolin is 10~100nm; In step A1, the mass ratio of silicon dioxide to aluminum oxide in the kaolin is 1:(1.8~2.2); In step A1, the iron oxide content in the kaolin is less than or equal to 0.5 wt%. In step A1, the kaolin has a Zeta potential of -20 to -40 mV at pH 7.

0.

3. The method according to claim 1, characterized in that, It has at least one of the following characteristics: In step A2, the alkali is at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonia, and tetramethylammonium hydroxide. In step A2, the concentration of the alkali is 0.05~0.2 mol / L; In step A2, the mass ratio of the alkali to the kaolin is 1:(5~20); In step A2, the temperature for alkaline treatment is 20~40℃; In step A2, the duration of alkali treatment is 0.5 to 2 hours; In step A2, the stirring speed when using alkali treatment is 100~600 rpm; In step A2, after the kaolin is treated with alkali, the clear liquid is removed and the solid is taken.

4. The method according to claim 1, characterized in that, It has at least one of the following characteristics: In step A3, the acid is at least one of acetic acid, hydrochloric acid, phosphoric acid, and citric acid; In step A3, the concentration of the acid is 1~3 mol / L; In step A3, the mass ratio of the acid to the kaolin is 1:(10~30); In step A3, the temperature for acid treatment is 20~40℃; In step A3, the duration of acid treatment is 0.5 to 2 hours; In step A3, the stirring speed when using acid treatment is 100~600 rpm; In step A3, after the acid treatment is completed, the modified kaolin with a pH of 6.8 to 7.2 is obtained.

5. The method according to claim 1, characterized in that, It has at least one of the following characteristics: In step S2, the mass ratio of the modified kaolin to chylous plasma is 1:(8~10); In step S2, the mixing speed of the modified kaolin and chylous plasma is 100~800 rpm; In step S2, the modified kaolin and chylous plasma are mixed at 20-40°C. In step S2, the mixing time of the modified kaolin and chylous plasma is 1-2 hours. In step S2, the modified kaolin and chylous plasma are mixed and then left to stand for 1-2 hours.

6. The method according to claim 1, characterized in that, It has at least one of the following characteristics: In step S3, the outer pore size of the diatomaceous earth is 5~20μm; In step S3, the inner pore size of the diatomaceous earth is 0.1~1μm; In step S3, the outer Zeta potential of the diatomaceous earth is -10mV; In step S3, the inner Zeta potential of the diatomaceous earth is +20mV; In step S3, the diatomaceous earth is modified with an aminosilane coupling agent to modify the inner layer positive charge. In step S3, the diatomaceous earth is doped with nano-hydroxyapatite, and the amount of nano-hydroxyapatite doped is 5-10 wt% of the mass of the diatomaceous earth. In step S3, the outer layer of the diatomaceous earth is coated with polyethylene glycol.

7. The method according to claim 1, characterized in that, It has at least one of the following characteristics: In step S3, the filter with a multi-layer gradient structure includes a pre-filter layer, a transition layer, and a fine filter layer. In step S3, the filter with a multi-layer gradient structure has an asymmetric flow channel with an inlet diameter of 50 mm and an outlet diameter of 30 mm. In step S3, the filter with the multi-layer gradient structure has an initial pressure of 0.1 bar and a final pressure of 0.5 bar. In step S3, the filter with a multi-layer gradient structure operates at 4~40℃; In step S3, the filter with the multi-layer gradient structure operates at a flux of 450~550 L / m at 25°C. 2 ·h.

8. The method according to claim 7, characterized in that, It has at least one of the following characteristics: The diatomaceous earth in the pre-filtration layer has a pore size of 10~50μm; The diatomite in the transition layer has a pore size of 1~5μm; The diatomaceous earth in the fine filtration layer is 0.1~0.5μm thick; The thickness of the pre-filter layer is 2~5mm; The thickness of the transition layer is 1~3mm; The thickness of the fine filter layer is 0.5~1mm.

9. The method according to claim 8, characterized in that, A mesh grid is provided between the pre-filter layer and the transition layer. The mesh grid is made of polypropylene and has a pore size of 2 mm.

10. The method according to claim 8, characterized in that, The filter with a multi-layer gradient structure includes at least one filter element, and each filter element has a filtration area of ​​3-5 m². 2 .

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