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CN117982987B - Leukocyte filtering material and preparation method thereof - Google Patents

Leukocyte filtering material and preparation method thereof Download PDF

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Publication number
CN117982987B
CN117982987B CN202410397637.2A CN202410397637A CN117982987B CN 117982987 B CN117982987 B CN 117982987B CN 202410397637 A CN202410397637 A CN 202410397637A CN 117982987 B CN117982987 B CN 117982987B
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polydopamine
leukocyte
temperature plasma
nano hydroxyapatite
low
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CN117982987A (en
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丁一
卢礼兵
张兴美
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Sichuan Houpu Biotechnology Co ltd
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Sichuan Houpu Biotechnology Co ltd
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D39/00Filtering material for liquid or gaseous fluids
    • B01D39/14Other self-supporting filtering material ; Other filtering material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2239/00Aspects relating to filtering material for liquid or gaseous fluids
    • B01D2239/10Filtering material manufacturing

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  • Filtering Materials (AREA)

Abstract

The invention relates to a leukocyte filtering material and a preparation method thereof, and relates to the technical field of filtering materials, wherein the leukocyte filtering material comprises a hydrophobic base material and hydrophilic substances attached to the surface of the hydrophobic base material; the hydrophilic substances are obtained by carrying out low-temperature plasma treatment and grinding treatment on nano hydroxyapatite and polydopamine; the hydrophilic substances comprise the following raw materials in parts by weight: 88-110 parts of nano hydroxyapatite and 0.05-0.2 part of polydopamine. The invention takes nano hydroxyapatite and polydopamine with proper proportion as raw materials, and adopts low-temperature plasma surface modification treatment and grinding treatment, thereby effectively overcoming the problems of low platelet recovery rate and the like of single nano hydroxyapatite and providing a new thought for the preparation of leukocyte filtering materials.

Description

Leukocyte filtering material and preparation method thereof
Technical Field
The invention relates to the technical field of filter materials, in particular to a leukocyte filter material and a preparation method thereof.
Background
Blood is one of the essential substances necessary for maintaining human vital activities, and its components mainly include plasma and blood cells, which are further divided into erythrocytes, leukocytes and platelets. In blood transfusion treatment, in order to avoid side effects such as non-hemolytic fever reaction, virus cross infection, etc. caused by leukocytes, leukocytes in blood are often removed before blood transfusion. Therefore, providing a filter material that removes leukocytes from platelet rich plasma plays an important role in the clinical efficacy of platelet products.
At present, the main working principles of the method for removing the white blood cells in the blood are divided into two types: one is a centrifugal separation method for removing white blood cells by using a centrifugal separator by utilizing a difference in specific gravity of blood cell components; and a filter method in which white blood cells are removed by adhesion or adsorption using a filter material comprising a fiber aggregate such as nonwoven fabric or a porous structure having continuous pores. Among them, the filter method has been widely used because of its advantages of safety, simplicity, rapidness, high filtering rate, etc. The existing filtering device for removing the white blood cells consists of a plurality of filtering materials, but the existing white blood cell filtering materials such as nano hydroxyapatite have better effect on white blood cell filtering, but can not inhibit the adsorption of the blood platelets and even play a role in promoting adhesion, so that the recovery rate of the blood platelets is too low to meet the use requirement.
Disclosure of Invention
In order to solve the problems, the invention provides a leukocyte filtering material and a preparation method thereof.
The technical scheme provided by the invention is as follows:
In a first aspect, the present invention provides a leukocyte filter material comprising a hydrophobic substrate and a hydrophilic substance attached to the surface of the hydrophobic substrate; the hydrophilic substances are obtained by carrying out low-temperature plasma treatment and grinding treatment on nano hydroxyapatite and polydopamine;
The hydrophilic substances comprise the following raw materials in parts by weight: 88-110 parts of nano hydroxyapatite and 0.05-0.2 part of polydopamine.
Further, the weight ratio of the nano hydroxyapatite to the polydopamine is 1000:1.
Further, the hydrophilic substances comprise the following raw materials in parts by weight: 100 parts of nano hydroxyapatite and 0.1 part of polydopamine.
Further, the operating parameters of the low temperature plasma treatment include: the working gas is argon, the gas flow is 50-100 ml/min, the system pressure is 10-50 Pa, the current intensity is 12-18 mA, and the treatment time is 5-30 s.
Further, the current intensity was 15mA, and the treatment time was 12s.
Further, the working parameters of the grinding process include: the grinding speed is 50-100 rpm, and the grinding time is 5-10 min.
Further, the hydrophobic substrate comprises at least one of polybutylene terephthalate, polyurethane, polypropylene, and polyamide; the particle size of the nano hydroxyapatite is 20-100 nm, and the particle size of the polydopamine is 50-200 nm.
In a second aspect, the present invention provides a method for preparing the leukocyte filter material according to any one of the first aspects, comprising the steps of:
obtaining the hydrophilic substance;
dissolving the hydrophilic substance in a solvent to obtain a solution;
and (3) placing the hydrophobic substrate in the solution to sequentially infiltrate, take out and dry to obtain the leukocyte filtering material.
Further, the solvent includes acetone.
Further, the operating parameters of the infiltration include: the soaking time is 2-5 h.
Compared with the prior art, the technical scheme provided by the embodiment of the invention has at least the following advantages:
The invention provides a leukocyte filtering material, which takes nano-hydroxyapatite and polydopamine with proper proportion as raw materials, and adopts low-temperature plasma surface modification treatment and grinding treatment, thereby effectively overcoming the problems of low platelet recovery rate and the like of single nano-hydroxyapatite and providing a new thought for the preparation of the leukocyte filtering material.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the invention and together with the description, serve to explain the principles of the invention.
In order to more clearly illustrate the embodiments of the invention or the technical solutions of the prior art, the drawings which are used in the description of the embodiments or the prior art will be briefly described, and it will be obvious to a person skilled in the art that other drawings can be obtained from these drawings without inventive effort.
Fig. 1 is a flowchart of a method for preparing a leukocyte filter material according to the present invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Unless otherwise specifically indicated, the various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or may be prepared by existing methods.
In a first aspect, the present invention provides a leukocyte filter material comprising a hydrophobic substrate and a hydrophilic substance attached to the surface of the hydrophobic substrate; the hydrophilic substances are obtained by carrying out low-temperature plasma treatment and grinding treatment on nano hydroxyapatite and polydopamine;
The hydrophilic substances comprise the following raw materials in parts by weight: 88-110 parts of nano hydroxyapatite and 0.05-0.2 part of polydopamine.
The invention provides a leukocyte filtering material and a preparation method thereof, wherein nano hydroxyapatite and polydopamine with proper proportions are used as raw materials, and the problems of low platelet recovery rate and the like of single nano hydroxyapatite are effectively solved through low-temperature plasma surface modification treatment and grinding treatment, so that a new thought is provided for the preparation of the leukocyte filtering material.
In some specific embodiments, the parts by weight of the nano-hydroxyapatite may be 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, etc.
In some embodiments, the parts by weight of the polydopamine may be 0.05 parts, 0.06 parts, 0.07 parts, 0.08 parts, 0.09 parts, 0.10 parts, 0.11 parts, 0.12 parts, 0.13 parts, 0.14 parts, 0.15 parts, 0.16 parts, 0.17 parts, 0.18 parts, 0.19 parts, 0.20 parts, and the like.
In some embodiments, the weight ratio of the nanohydroxyapatite to the polydopamine is 1000:1.
The inventor researches and discovers that the obtained leukocyte filter material has better performance and higher platelet recovery rate by controlling the weight ratio of the nano hydroxyapatite to the polydopamine to be 1000:1. The two keep forward synergistic effect within a certain dosage range, and if the dosage of polydopamine is too large, the two show a certain antagonism, but the performance of the nano hydroxyapatite can be reduced.
In some specific embodiments, the hydrophilic substance comprises the following raw materials in parts by weight: 100 parts of nano hydroxyapatite and 0.1 part of polydopamine.
In some embodiments, the operating parameters of the low temperature plasma process include: the working gas is argon, the gas flow is 50-100 ml/min, the system pressure is 10-50 Pa, the current intensity is 12-18 mA, and the treatment time is 5-30 s.
In the present invention, the low temperature plasma treatment may be performed by using an existing low temperature plasma treatment apparatus, and is not particularly limited.
In some embodiments, the current intensity is 15mA and the treatment time is 12s.
In some embodiments, the operating parameters of the grinding process include: the grinding speed is 50-100 rpm, and the grinding time is 5-10 min. Preferably, the milling speed is 80rpm and the milling time is 8 minutes.
In some embodiments, the hydrophobic substrate comprises at least one of polybutylene terephthalate, polyurethane, polypropylene, and polyamide; the particle size of the nano hydroxyapatite is 20-100 nm, and the particle size of the polydopamine is 50-200 nm.
In the invention, the hydrophobic base material, the nano-hydroxyapatite and the polydopamine can be prepared directly by adopting commercial products or according to the existing preparation process, and are not particularly limited. Specifically, the nano hydroxyapatite may be self-made by using the prior art such as a hydrothermal method (a reaction of calcium salt and phosphate in an aqueous solution of a closed container at a relatively high pressure and temperature to synthesize hydroxyapatite), a chemical precipitation method (a reaction of calcium salt and phosphate in an aqueous solution to produce hydroxyapatite), or may be commercially available nano hydroxyapatite such as wuhan Hua Xiangke, wuhan han white pharmaceutical chemicals, etc., with an active ingredient content of 99.9% and a specification of 20nm, 50nm, etc. The polydopamine can be self-made according to the prior art such as the existing oxidative polymerization method (polymerizing dopamine into polydopamine through oxidative polymerization under alkaline conditions), the self-template method (forming polydopamine through oxidative polymerization by using dopamine itself as a reaction template), the preparation method of the nano polydopamine with controllable size disclosed in the prior art (patent number 201911147981.1), or the commercially available polydopamine such as the Siemens Ji Yue organism can be adopted.
In a second aspect, based on the same inventive concept, the present invention provides a method for preparing the leukocyte filter material according to any one of the first aspects, as shown in fig. 1, comprising the steps of:
obtaining the hydrophilic substance;
dissolving the hydrophilic substance in a solvent to obtain a solution;
and (3) placing the hydrophobic substrate in the solution to sequentially infiltrate, take out and dry to obtain the leukocyte filtering material.
The invention provides a preparation method of a leukocyte filtering material, which is simple to operate, does not need extra specific equipment and is suitable for batch industrial production. Meanwhile, the preparation method is realized based on the technical scheme of any one of the first aspect, so that the preparation method has at least the beneficial effects of the first aspect, and is not repeated herein.
In some embodiments, the solvent comprises acetone.
In some embodiments, the operating parameters of the infiltration include: the soaking time is 2-5 h.
The white blood cell filter material and the raw materials related to the preparation method thereof can be prepared by adopting commercial products or according to the existing preparation process if no special limitation or specific description exists; meanwhile, the related operation steps and parameter conditions can be carried out according to the technology disclosed by the prior art or by adopting the prior equipment if no special limitation or specific description exists, and the invention file is not repeated one by one.
The invention will be further illustrated with reference to specific examples. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. The experimental procedures, which are not specified in the following examples, are generally determined according to national standards. If the corresponding national standard does not exist, the method is carried out according to the general international standard, the conventional condition or the condition recommended by the manufacturer.
Example 1
The embodiment provides a leukocyte filtering material, which comprises a hydrophobic base material and hydrophilic substances attached to the surface of the hydrophobic base material; the hydrophobic substrate is a polybutylene terephthalate substrate non-woven fabric, and the average pore diameter is 12 mu m; the hydrophilic substance is obtained by carrying out low-temperature plasma treatment and grinding treatment on nano hydroxyapatite and polydopamine with the weight ratio of 1000:1; the hydrophilic substances comprise the following raw materials in parts by weight: 100 parts of nano hydroxyapatite with the particle size of 50nm and 0.1 part of polydopamine with the particle size of 100 nm.
The preparation method of the leukocyte filter material comprises the following steps:
Step (1): uniformly mixing nano hydroxyapatite and polydopamine, and placing the mixture in a cavity of low-temperature plasma treatment equipment, wherein the tiled thickness is 2-3 mm; adjusting the distance between two polar plates of low-temperature plasma treatment equipment to be 50mm, vacuumizing to enable the pressure in the cavity to be 40Pa, and performing low-temperature plasma treatment for 10s under the conditions that the current intensity is 15mA and argon with the gas flow of 80ml/min is used as working gas to obtain a modified composite material;
Step (2): grinding the modified composite material obtained in the step (1) at a grinding speed of 80rpm for 8min to obtain hydrophilic substances;
step (3): dissolving the hydrophilic substance obtained in the step (2) in acetone, and stirring and mixing to obtain a solution with the weight concentration of the hydrophilic substance of 3 wt%;
Step (4): and (3) placing the hydrophobic substrate in the solution obtained in the step (3) to be sequentially soaked for 5 hours, taking out and drying to obtain the leukocyte filtering material.
Example 2
The embodiment provides a leukocyte filtering material, which comprises a hydrophobic base material and hydrophilic substances attached to the surface of the hydrophobic base material; the hydrophobic substrate is a polybutylene terephthalate substrate non-woven fabric, and the average pore diameter is 12 mu m; the hydrophilic substance is obtained by carrying out low-temperature plasma treatment and grinding treatment on nano hydroxyapatite and polydopamine with the weight ratio of 1760:1; the hydrophilic substances comprise the following raw materials in parts by weight: 88 parts of nano hydroxyapatite with the particle size of 50nm and 0.05 part of polydopamine with the particle size of 100 nm.
The preparation method of the leukocyte filter material comprises the following steps:
Step (1): uniformly mixing nano hydroxyapatite and polydopamine, and placing the mixture in a cavity of low-temperature plasma treatment equipment, wherein the tiled thickness is 2-3 mm; adjusting the distance between two polar plates of low-temperature plasma treatment equipment to be 50mm, vacuumizing to enable the pressure in the cavity to be 10Pa, and performing low-temperature plasma treatment for 30s under the conditions that the current intensity is 12mA and argon with the gas flow of 50ml/min is used as working gas to obtain a modified composite material;
step (2): grinding the modified composite material obtained in the step (1) at a grinding speed of 50rpm for 10min to obtain hydrophilic substances;
step (3): dissolving the hydrophilic substance obtained in the step (2) in acetone, and stirring and mixing to obtain a solution with the weight concentration of the hydrophilic substance of 3 wt%;
Step (4): and (3) placing the hydrophobic substrate in the solution obtained in the step (3) to be sequentially soaked for 5 hours, taking out and drying to obtain the leukocyte filtering material.
Example 3
The embodiment provides a leukocyte filtering material, which comprises a hydrophobic base material and hydrophilic substances attached to the surface of the hydrophobic base material; the hydrophobic substrate is a polybutylene terephthalate substrate non-woven fabric, and the average pore diameter is 12 mu m; the hydrophilic substance is obtained by carrying out low-temperature plasma treatment and grinding treatment on nano hydroxyapatite and polydopamine with the weight ratio of 550:1; the hydrophilic substances comprise the following raw materials in parts by weight: 110 parts of nano hydroxyapatite with the particle size of 50nm and 0.2 part of polydopamine with the particle size of 100 nm.
The preparation method of the leukocyte filter material comprises the following steps:
Step (1): uniformly mixing nano hydroxyapatite and polydopamine, and placing the mixture in a cavity of low-temperature plasma treatment equipment, wherein the tiled thickness is 2-3 mm; adjusting the distance between two polar plates of low-temperature plasma treatment equipment to be 50mm, vacuumizing to enable the pressure in the cavity to be 50Pa, and performing low-temperature plasma treatment for 5s under the conditions that the current intensity is 18mA and argon with the gas flow of 100ml/min is used as working gas to obtain a modified composite material;
step (2): grinding the modified composite material obtained in the step (1) at a grinding speed of 100rpm for 5min to obtain hydrophilic substances;
step (3): dissolving the hydrophilic substance obtained in the step (2) in acetone, and stirring and mixing to obtain a solution with the weight concentration of the hydrophilic substance of 3 wt%;
Step (4): and (3) placing the hydrophobic substrate in the solution obtained in the step (3) to be sequentially soaked for 5 hours, taking out and drying to obtain the leukocyte filtering material.
Example 4
This example provides a leukocyte filter material and a method for producing the same, which differ from example 2 only in that: adjusting the consumption of polydopamine to 0.088 parts; the rest steps and parameters are the same.
Comparative example 1
This example provides a leukocyte filter material and a method for producing the same, which differ from example 1 only in that: adjusting the amount of polydopamine to 0 parts (i.e. polydopamine is not added); the rest steps and parameters are the same.
Comparative example 2
This example provides a leukocyte filter material and a method for producing the same, which differ from example 1 only in that: adjusting the consumption of the polydopamine to 0.5 part (namely, the adding amount of the polydopamine is excessive); the rest steps and parameters are the same.
Comparative example 3
This example provides a leukocyte filter material and a method for producing the same, which differ from example 1 only in that: the hydrophilic substance is obtained by directly grinding and mixing nano hydroxyapatite and polydopamine (i.e. without low-temperature plasma treatment); the rest steps and parameters are the same.
Test case
The leukocyte filter materials provided in the examples and comparative examples were subjected to performance tests.
The testing method comprises the following steps: the platelet-rich plasma is prepared by taking whole blood of healthy voluntary blood donors, and then the platelet-rich plasma is collected by the leukocyte filtering materials provided by the examples and the comparative examples under the action of gravity, so as to obtain the platelet-rich plasma with leukocytes removed. Recording the platelet capacities before and after filtration, performing blood cell count on the blood samples before and after filtration by using a blood cell analyzer, and calculating according to a formula (I) to obtain the platelet recovery rate; counting the white blood cells in the blood samples before and after filtration by using a Nageotte white blood cell counting plate, and calculating according to a formula (II) to obtain a white blood cell filtration rate, wherein the test result is shown in Table 1;
the formula (one): platelet recovery (%) = C 1/C2 ×100%; wherein, C 1 is the number of platelets contained in the unit volume of blood sample after filtration, and C 2 is the number of platelets contained in the unit volume of blood sample before filtration;
The formula (II): leukocyte removal rate (%) = (C 3-C4)/C3 ×100%; where C 3 is the number of leukocytes contained in the unit volume of blood sample before filtration, and C 4 is the number of leukocytes contained in the unit volume of blood sample after filtration).
TABLE 1
As can be seen from table 1: compared with the comparative example, the leukocyte filtering material provided by the embodiment of the invention has higher leukocyte filtering rate and platelet recovery rate, the leukocyte filtering material obtained by the embodiment 1 has the best effect, the leukocyte filtering rate can reach 99.99 percent, and the platelet recovery rate can reach 93.1 percent, which proves that the invention effectively inhibits the adhesion behavior of nano hydroxyapatite to platelets by adopting the nano hydroxyapatite and polydopamine with proper proportion for compounding and matching with the treatment steps of low-temperature plasma surface modification and the like, thereby overcoming the problems of low platelet recovery rate and the like of single nano hydroxyapatite. In addition, the hemolysis rate of the leukocyte filtering material provided by the embodiment of the invention is lower than 3% by the experiment measurement, so that the use requirement is met.
In summary, the invention provides a leukocyte filtering material and a preparation method thereof, which effectively overcomes the problems of low platelet recovery rate and the like of single nano hydroxyapatite by adopting nano hydroxyapatite and polydopamine with proper proportion as raw materials and carrying out low-temperature plasma surface modification treatment and grinding treatment, and provides a new thought for the preparation of the leukocyte filtering material.
Various embodiments of the invention may exist in a range of forms; it should be understood that the description in a range format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the invention; it is therefore to be understood that the range description has specifically disclosed all possible sub-ranges and individual values within that range. For example, it should be considered that a description of a range from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the range, such as 1,2, 3, 4,5, and 6, wherever applicable. In addition, whenever a numerical range is referred to herein, it is meant to include any reference number (fractional or integer) within the indicated range.
The foregoing is only a specific embodiment of the invention to enable those skilled in the art to understand or practice the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (1)

1. A leukocyte filtering material, characterized in that it comprises a hydrophobic base material and a hydrophilic substance attached to the surface of the hydrophobic base material; the hydrophobic substrate is a polybutylene terephthalate substrate non-woven fabric, and the average pore diameter is 12 mu m; the hydrophilic substance is obtained by carrying out low-temperature plasma treatment and grinding treatment on nano hydroxyapatite and polydopamine with the weight ratio of 1000:1; the hydrophilic substances comprise the following raw materials in parts by weight: 100 parts of nano hydroxyapatite with the particle size of 50nm and 0.1 part of polydopamine with the particle size of 100 nm;
the preparation method of the leukocyte filter material comprises the following steps:
Step (1): uniformly mixing nano hydroxyapatite and polydopamine, and placing the mixture in a cavity of low-temperature plasma treatment equipment, wherein the tiled thickness is 2-3 mm; adjusting the distance between two polar plates of low-temperature plasma treatment equipment to be 50mm, vacuumizing to enable the pressure in the cavity to be 40Pa, and performing low-temperature plasma treatment for 10s under the conditions that the current intensity is 15mA and argon with the gas flow of 80ml/min is used as working gas to obtain a modified composite material;
Step (2): grinding the modified composite material obtained in the step (1) at a grinding speed of 80rpm for 8min to obtain hydrophilic substances;
step (3): dissolving the hydrophilic substance obtained in the step (2) in acetone, and stirring and mixing to obtain a solution with the weight concentration of the hydrophilic substance of 3 wt%;
Step (4): and (3) placing the hydrophobic substrate in the solution obtained in the step (3) to be sequentially soaked for 5 hours, taking out and drying to obtain the leukocyte filtering material.
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