CN115845822A - Adsorbing material for removing blood cell factor and preparation method thereof - Google Patents
Adsorbing material for removing blood cell factor and preparation method thereof Download PDFInfo
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Abstract
The application discloses an adsorbing material for removing blood cytokines and a preparation method thereof, belonging to the field of biomedical materials. An adsorbing material for removing blood cell factors comprises an adsorbing carrier, wherein the adsorbing carrier is grafted with alkyl methacrylate, and the adsorbing carrier is fixedly loaded with acetylated cysteine, acetylated glycyrrhizic acid or a combination of the acetylated cysteine and the acetylated glycyrrhizic acid. The preparation method comprises the following steps: grafting alkyl methacrylate on the adsorption carrier, carrying out epoxidation, carrying out amination reaction on the obtained epoxy product and a polyamine compound to form an amino connecting arm, carrying out condensation reaction on the amino connecting arm and cysteine and/or glycyrrhizic acid, and carrying out acetylation reaction on the cysteine and/or glycyrrhizic acid to prepare the adsorption material for removing the blood cell factors. The application has better effect of clearing inflammatory cytokines in blood.
Description
Technical Field
The application relates to the field of biomedical materials, in particular to an adsorbing material for removing blood cytokines and a preparation method thereof.
Background
Cytokines help stimulate and regulate the immune system to help the body fight infections, but if overproduction occurs in the body, autoimmune diseases develop. Cytokine storms, which are phenomena that cause rapid and massive production of various cytokines in body fluids after the body is infected with microorganisms, actually cause or aggravate diseases. Cytokine storms are also a significant cause of acute respiratory distress syndrome, multiple organ failure and life threatening sepsis, severe burns, trauma, pancreatitis, lung injury, etc.
The blood perfusion technology is commonly used for removing toxins and pathogenic substances in blood clinically, so that the aims of purifying the blood, and relieving and treating diseases are fulfilled. In the course of treatment, the removal of inflammatory cytokines (represented by IL-6) is a difficult problem in the study of blood perfusion techniques, which can remove molecular toxins from the body of critically ill patients, but the removal rate of inflammatory cytokines is still not ideal.
At present, most of domestic hemoperfusion products adopt polystyrene divinyl benzene as an adsorbent, are poor in blood compatibility, have low adsorption rate on inflammatory cytokines, and cannot be used for adsorbing and removing the inflammatory cytokines and treating critical diseases.
Disclosure of Invention
In order to better eliminate inflammatory cytokines in blood, the application provides an adsorption material for eliminating the blood cytokines and a preparation method thereof.
In a first aspect, the adsorption material for removing blood cytokines provided by the present application adopts the following technical scheme:
the adsorption material for removing the blood cytokines comprises an adsorption carrier, wherein alkyl methacrylate is grafted on the adsorption carrier, and the adsorption carrier is fixedly loaded with acetylated cysteine, acetylated glycyrrhizic acid or a combination of the acetylated cysteine and the acetylated glycyrrhizic acid.
By adopting the technical scheme, the hydrophobic characteristic of the alkyl methacrylate is fully utilized, and the alkyl methacrylate is grafted on the adsorption carrier, most of the matched cytokines contain hydrophobic structures, and the hydrophobic characteristic of the alkyl methacrylate is similar to that of the cytokines, so that the adsorption effect of the adsorption material on the cytokines is enhanced.
The cysteine plays a role in weakening the protein structure of the inflammatory cytokines and increases the contact area of the polystyrene divinylbenzene microspheres and the inflammatory cytokines, thereby improving the capability of removing the inflammatory cytokines. The acetylation is carried out on the cysteine, so that the hydrophilicity of the adsorbing material is improved, the amido bond is increased, and the recognition capability and the adsorption selectivity of the adsorbing material on inflammatory cytokines are effectively improved. Inflammation and allergy can reduce thiol enzyme such as cholinesterase, and thiol group on ligand cysteine can maintain activity of thiol enzyme, thereby improving inflammation and allergic skin symptoms.
Glycyrrhizic acid is the main component of the licorice root extract, the glycyrrhizic acid can regulate the expression and release of various cytokines and play an anti-inflammatory role, and the acetylated glycyrrhizic acid has a more significant anti-inflammatory role.
In addition, the acetylated cysteine and the acetylated glycyrrhizic acid are matched and immobilized, and can synergistically play a better role in adsorbing inflammatory cytokines on the basis of alkyl methacrylate grafting, so that the effect of removing the inflammatory cytokines in blood is more obvious.
Optionally, the adsorption carrier is one or two of polystyrene divinyl benzene microspheres and polymethyl methacrylate resin microspheres.
By adopting the technical scheme, the polystyrene divinyl benzene microspheres and the polymethyl methacrylate resin microspheres are both adsorption resins with residual double bonds, and can be used for grafting alkyl methacrylate and immobilizing cysteine and glycyrrhizic acid to form adsorption materials.
Optionally, the number of carbon atoms in the alkyl group of the alkyl methacrylate is twelve or more.
By adopting the technical scheme, the long-chain alkyl methacrylate is taken as the hydrophobic chain segment, and the compatibility with the cytokine is high, so that the adsorption effect of the adsorption material on the cytokine is enhanced.
Optionally, the alkyl methacrylate is lauryl methacrylate.
Optionally, the adsorption carrier is a polystyrene divinylbenzene microsphere, the pore diameter of the polystyrene divinylbenzene microsphere is 2 to 50nm, and the specific surface area of the polystyrene divinylbenzene microsphere is 500 to 1000m 2 /g。
By adopting the technical scheme, the polystyrene divinyl benzene microspheres meeting the pore size range and the specific surface area range have good effect of grafting the alkyl methacrylate, high adsorption capacity and excellent effect on inflammatory cytokines in blood.
Optionally, the adsorption carrier is loaded with a combination of acetylated cysteine and acetylated glycyrrhizic acid, and the weight ratio of cysteine to glycyrrhizic acid is 1 (0.2 to 3).
By adopting the technical scheme, the acetylated cysteine and the acetylated glycyrrhizic acid are compatible and immobilized according to the proportion, so that the effects of the cysteine and the glycyrrhizic acid are exerted, and the cysteine and the glycyrrhizic acid can possibly react, therefore, the synergistic effect is obvious, and the clearance rate of the adsorption material to inflammatory cytokines is obviously improved.
Optionally, the acylating agent used for the acetylated cysteine and the acetylated glycyrrhizic acid is one or two of acetic acid and acetyl chloride.
Optionally, the acetylation reaction is carried out by adding an acylating agent and a catalyst after the cysteine and/or glycyrrhizic acid is immobilized on the adsorption carrier, wherein the catalyst is preferably 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and the reaction condition is shaking.
Optionally, the adsorption carrier further comprises one or more of polymyxin B sulfate, polylysine and polyethyleneimine.
By adopting the technical scheme, the polymyxin B sulfate, the polylysine and the polyethyleneimine have broad-spectrum antibacterial activity and have adsorption and removal effects on negatively charged endotoxin, and the immobilized ligand with the endotoxin removal effect is combined by utilizing the reaction of the glycyrrhizic acid immobilized in the adsorption carrier and the polymyxin B sulfate, the polylysine or the polyethyleneimine, so that the blood perfusion adsorption material capable of simultaneously removing inflammatory cytokines and the endotoxin is obtained.
Optionally, the polylysine has a molecular weight of 3600-4300 and the polyethyleneimine has a molecular weight of 1800-10000.
Optionally, the adsorption carrier is connected to the amino connecting arm through a polyamine compound, and the adsorption carrier is used for immobilizing the acetylated cysteine, the acetylated glycyrrhizic acid or the combination of the acetylated cysteine and the acetylated glycyrrhizic acid through the amino connecting arm.
By adopting the technical scheme, the amino connecting arm is used as a connecting bridge between the cysteine and the glycyrrhizic acid and the adsorption carrier, so that the immobilization of the acetylated cysteine and the acetylated glycyrrhizic acid is realized.
Optionally, the polyamine compound is one or both of hexamethylene diamine and pentamethylene diamine.
Optionally, before the adsorption carrier is connected to the amino connecting arm, an epoxidation reaction is performed.
By adopting the technical scheme, the polyamine compound is accessed through the epoxidation reaction so as to realize the access of the amino connecting arm.
Optionally, an oxidizing agent is used in the epoxidation reaction to epoxidize the residual double bonds in the adsorption carrier to obtain epoxy groups, the oxidizing agent is preferably m-chloroperoxybenzoic acid, and the reaction condition is low-temperature stirring.
Optionally, the adsorption carrier is grafted to the amino linking arm through an amination reaction, the amination reaction adopts a polyamine compound to react with an epoxy group of the adsorption carrier, so that the adsorption carrier obtains an amino group, and the reaction condition is heating oscillation.
Optionally, the cysteine and/or glycyrrhizic acid is/are immobilized on the adsorption carrier through a condensation reaction, the condensation reaction is that the cysteine and/or glycyrrhizic acid reacts with the amine group of the adsorption carrier, a catalyst is added in a matching manner, the catalyst is preferably N-hydroxysuccinimide and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and the reaction condition is oscillation.
In a second aspect, the preparation method of the adsorbing material for removing blood cytokines provided by the present application adopts the following technical scheme:
grafting alkyl methacrylate on the adsorption carrier, carrying out epoxidation reaction, carrying out amination reaction on the obtained epoxy product and a polyamine compound to form an amino connecting arm, carrying out condensation reaction on the amino connecting arm and cysteine and/or glycyrrhizic acid, and carrying out acetylation reaction on the cysteine and/or glycyrrhizic acid to prepare the adsorption material for removing the blood cell factors.
By adopting the technical scheme, alkyl methacrylate is grafted to form a hydrophobic chain segment, an amino connecting arm is obtained through epoxidation reaction and amination reaction and is used for immobilizing cysteine and glycyrrhizic acid, and the adsorption and removal capacity of cysteine and glycyrrhizic acid on inflammatory cytokines is improved through acetylation reaction.
In summary, the present application has the following beneficial effects:
1. the hydrophobic characteristic of the alkyl methacrylate is compatible with the cytokine, so that the adsorption effect of the adsorption material on the cytokine is enhanced; cysteine plays a role in weakening the protein structure of the inflammatory cytokine and increases the contact area of the polystyrene divinyl benzene microspheres and the inflammatory cytokine, so that the capability of removing the inflammatory cytokine is improved; the glycyrrhizic acid is the main component of the licorice root extract, the glycyrrhizic acid can regulate the expression and release of various cytokines and play an anti-inflammatory role, and the acetylated cysteine and the acetylated glycyrrhizic acid are matched and immobilized to cooperatively play a better inflammatory cytokine adsorption role, so that the effect of removing inflammatory cytokines in blood is more obvious.
2. The application also utilizes the reaction of the grafted glycyrrhizic acid and polymyxin B sulfate, polylysine or polyethyleneimine to form an immobilized ligand, and obtains good endotoxin adsorption and removal effects, so that the adsorption material has the function of removing inflammatory cytokines and endotoxin.
Detailed Description
The present application is described in further detail below.
Examples
Example 1
The preparation method of the adsorbing material for removing the blood cytokines comprises the following steps:
s1, grafting:
taking 10g of polystyrene divinyl benzene microspheres (the aperture is 2-50nm, and the specific surface area is 500-1000m) 2 Adding 10wt% of lauryl methacrylate ethanol solution 50mL, adding 1g of potassium persulfate, stirring and reacting at 60 ℃ for 6h, wherein the stirring speed is 200rpm, and introducing nitrogen in the reaction process; after the reaction is finished, the adsorbent A1 is obtained by washing with ethanol and water and drying.
S2, solid loading:
adding 10g of adsorbent A1 into 40mL of dichloroethane, soaking overnight, adding 20mL of dichloroethane solution of 1wt% m-chloroperoxybenzoic acid, stirring in an ice-water bath for reaction for 24 hours, and carrying out epoxidation reaction at the rotating speed of 250 rpm; and after the reaction is finished, washing with ethanol and water, and drying to obtain an epoxy product.
Adding the epoxy product into 40mL of 2wt% hexamethylene diamine aqueous solution, and carrying out oscillation reaction at 60 ℃ for 24 hours to carry out amination reaction; after the reaction is finished, washing the reaction product by using ethanol and water, and drying the reaction product to obtain an amination product.
Taking 10g of amination product, adding 30mL of 1.2wt% cysteine solution, adjusting the pH value to 4.8, adding 0.6g of N-hydroxysuccinimide, slowly adding 0.4g of 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride, carrying out oscillation reaction at 25 ℃ for 5h, and carrying out condensation reaction; and after the reaction is finished, washing with ethanol and water, and drying to obtain a condensation product.
Adding 30mL of 0.6% acetic acid solution into the condensation product, adjusting the pH value to 4.8, slowly adding 0.5g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, carrying out oscillation reaction at 30 ℃ for 4h, and carrying out acetylation reaction; and after the reaction is finished, washing with ethanol and water, and drying to obtain the adsorbent B1.
Example 2
The preparation method of the adsorbing material for removing the blood cytokines comprises the following steps:
s1, grafting:
taking polystyrene diethyl ether10g of alkenyl benzene microsphere (the aperture is 2 to 50nm, and the specific surface area is 500 to 1000m) 2 Adding 10wt% of lauryl methacrylate ethanol solution 50mL, adding 1g of potassium persulfate, stirring and reacting at 60 ℃ for 6h, wherein the stirring speed is 200rpm, and introducing nitrogen in the reaction process; and after the reaction is finished, washing with ethanol and water, and drying to obtain the adsorbent A2.
S2, solid loading:
adding 10g of adsorbent A2 into 40mL of dichloroethane, soaking overnight, adding 20mL of dichloroethane solution of 1wt% m-chloroperoxybenzoic acid, stirring in an ice-water bath for reaction for 24 hours, and carrying out epoxidation reaction at the rotating speed of 250 rpm; and after the reaction is finished, washing with ethanol and water, and drying to obtain an epoxy product.
Adding the epoxy product into 40mL of 2wt% hexamethylene diamine aqueous solution, and carrying out oscillation reaction at 60 ℃ for 24 hours to carry out amination reaction; and after the reaction is finished, washing with ethanol and water, and drying to obtain an amination product.
Taking 10g of aminated product, adding 30mL of 1.2wt% of glycyrrhizic acid solution, adjusting the pH value to 4.8, adding 0.6g of N-hydroxysuccinimide, slowly adding 0.4g of 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride, carrying out oscillation reaction at 25 ℃ for 5h, and carrying out condensation reaction; and after the reaction is finished, washing with ethanol and water, and drying to obtain a condensation product.
Adding 30mL of 0.6% acetic acid solution into the condensation product, adjusting the pH value to 4.8, slowly adding 0.5g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, carrying out oscillation reaction at 30 ℃ for 4h, and carrying out acetylation reaction; and after the reaction is finished, washing with ethanol and water, and drying to obtain the adsorbent B2.
Example 3
The difference between this embodiment and embodiment 1 is that s2. The immobilization step specifically includes:
taking 10g of amination product, adding 30mL of 1.2wt% of cysteine and 1.2wt% of glycyrrhizic acid solution, adjusting the pH to 4.8, adding 0.6g of N-hydroxysuccinimide, slowly adding 0.4g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, carrying out oscillation reaction at 25 ℃ for 5h, and carrying out condensation reaction; and after the reaction is finished, washing with ethanol and water, and drying to obtain a condensation product.
Adding 30mL of 0.6% acetic acid solution into the condensation product, adjusting the pH value to 4.8, slowly adding 0.5g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, carrying out oscillation reaction at 30 ℃ for 4h, and carrying out acetylation reaction; and after the reaction is finished, washing with ethanol and water, and drying to obtain the adsorbent B3.
Example 4
The difference between this example and example 3 is that, in the condensation reaction, 2wt% of cysteine and 0.4wt% of glycyrrhizic acid were added to the solution, and finally, an adsorbent B4 was obtained.
Example 5
This example is different from example 3 in that in the condensation reaction, 0.6% by mass of cysteine and 1.8% by mass of glycyrrhizic acid were added to the solution, and an adsorbent B5 was finally obtained.
Example 6
This embodiment is different from embodiment 3 in that the S3 step is provided after the S2 step.
S3: adding 50mL of 3wt% polymyxin B sulfate solution into the adsorbent B3 prepared in example 3, and reacting at 40 ℃ for 24h; and after the reaction is finished, washing with ethanol and water, and drying to obtain the adsorbent C6.
Example 7
This embodiment is different from embodiment 3 in that the step S4 is provided after the step S3.
S3: 50mL of a 3wt% polylysine solution is added into the adsorbent B3 prepared in the example 3, and the mixture reacts for 24 hours at the temperature of 40 ℃; and after the reaction is finished, washing with ethanol and water, and drying to obtain the adsorbent C7.
Example 8
This embodiment is different from embodiment 3 in that the step S4 is provided after the step S3.
S3: adding 50mL of 3wt% polyethyleneimine solution into the adsorbent B3 prepared in example 3, and reacting at 40 ℃ for 24h; and after the reaction is finished, washing the reaction product by using ethanol and water, and drying the reaction product to obtain an adsorbent C8.
Comparative example
Comparative example 1
The present comparative example differs from example 3 in that the present comparative example does not have the step S1, and the adsorbent A1 is replaced with 10g of polystyrene divinylbenzene microspheres in the step S2 to finally obtain the adsorbent N1.
Effect detection
1. Experiment for adsorbing inflammatory cytokines
Taking a pyrogen-free test tube, respectively adding 0.25mL of the prepared adsorbent, then adding 2.5mL of blood plasma containing 141.0pg/mL of inflammatory cytokine interleukin-6 (IL-6), carrying out shock adsorption for 2 hours (the temperature is 37 ℃, the shock rate is 100 +/-10 rpm), then detecting the concentration of IL-6, and calculating the clearance rate of the adsorbent to the IL-6, wherein the results are shown in Table 1.
TABLE 1
| Adsorbent and process for producing the same | Pre-adsorption concentration (pg/mL) | Post-adsorption concentration (pg/mL) | Clearance (%) |
| Polystyrene divinyl benzene microspheres | 141 | 95.90 | 32.0 |
| A1 | 141 | 78.10 | 44.6 |
| B1 | 141 | 62.60 | 55.6 |
| B2 | 141 | 68.81 | 51.2 |
| B3 | 141 | 39.60 | 71.9 |
| B4 | 141 | 41.06 | 70.9 |
| B5 | 141 | 39.95 | 71.7 |
| C6 | 141 | 40.61 | 71.2 |
| C7 | 141 | 37.37 | 73.5 |
| C8 | 141 | 45.12 | 68.0 |
| N1 | 141 | 57.23 | 59.4 |
As can be seen from table 1, the clearance of inflammatory cytokines (represented by IL-6) was only 32% when polystyrene divinylbenzene microspheres were used as the adsorption carriers, and the clearance was increased to 40% or more when lauryl methacrylate was grafted. After the adsorption carrier is used for immobilizing the acetylated cysteine or the acetylated glycyrrhizic acid, the removal capacity of inflammatory cytokines can be improved to more than 50%, and the removal rate of the immobilized acetylated cysteine and the glycyrrhizic acid is obviously improved to more than 70%, so that the immobilization of the cysteine and the glycyrrhizic acid has a certain synergistic effect on the adsorption and removal of IL-6.
In addition, after the immobilized glycyrrhizic acid is used for enabling polymyxin B sulfate, polylysine or polyethyleneimine to form the immobilized ligand, the adsorbing material can still keep good inflammatory cytokine clearance rate, wherein polylysine is used as the immobilized ligand to play a role in improving the clearance rate.
2. Experiment for adsorbing endotoxin
Endotoxin concentration of patients with high endotoxin is generally less than 1EU/mL, and the initial adsorption concentration is set to be 1EU/mL in experiments. Taking a pyrogen-free test tube, respectively adding 0.05g of the prepared adsorbent, adding 1.5mL of a solution containing 1EU/mL of endotoxin, carrying out vibration adsorption for 2 hours (the temperature is 37 ℃, the vibration speed is 100 +/-10 rpm), measuring the concentration of the adsorbed endotoxin by using a chromogenic substrate limulus kit, and calculating the clearance rate of the adsorbent to the adsorbed endotoxin, wherein the results are shown in Table 2.
TABLE 2
| Adsorbent and method of making same | Concentration before adsorption (EU/mL) | Concentration after adsorption (EU/mL) | Clearance (%) |
| A1 | 1.0 | 0.98 | 2 |
| B1 | 1.0 | 0.99 | 1 |
| B2 | 1.0 | 0.98 | 2 |
| B3 | 1.0 | 0.95 | 5 |
| B4 | 1.0 | 0.97 | 3 |
| B5 | 1.0 | 0.98 | 2 |
| C6 | 1.0 | 0.42 | 58 |
| C7 | 1.0 | 0.34 | 66 |
| C8 | 1.0 | 0.46 | 54 |
| N1 | 1.0 | 0.98 | 2 |
As can be seen from the table 2, the adsorbing material has a good adsorption effect on endotoxin after being acted by polymyxin B sulfate, polylysine or polyethyleneimine, so that the clearance rate of the adsorbing material on the endotoxin is greatly improved.
3. Hemolysis test
The adsorption materials prepared in examples 1 to 8 were used to measure the hemolysis rate (in the hemolysis test, the hemolysis test was performed according to GB/T16886.4-2003, section 4 of test selection for biological evaluation of medical instruments for interaction with blood, GB/T16175-2008, test method for biological evaluation of medical silicone materials).
5g of the sample is added into each tube of the sample group, and 10ml of sodium chloride injection is added into each tube of the sample group, 10ml of sodium chloride injection is added into each tube of the negative control group, and 10ml of distilled water is added into each tube of the positive control group. Each set of 3 tubes was run in parallel. Placing all test tubes in constant temperature water bath (37 + -1) deg.C, keeping the temperature for 30min, adding 0.2ml diluted rabbit blood into each test tube, mixing, and placing in water bath (37 + -1) deg.C for continuously keeping the temperature for 60 min. The liquid in the pouring tube was centrifuged at 800g for 5 min. The supernatant was pipetted into a cuvette and the absorbance was measured with a spectrophotometer at 545 nm. The absorbance of the sample combination control group was averaged over 3 tubes. The absorbance of the negative control tube should not be greater than 0.03, the absorbance of the positive control tube should be 0.8 + -0.3, otherwise, the test should be repeated.
Wherein A is sample set absorbance;
b-absorbance of negative control group;
c-absorbance of positive control group.
The hemolysis rate of the obtained adsorbing material is less than 5 percent and meets the national standard requirement.
This detailed description is to be construed as illustrative only and is not limiting, and modifications of the detailed description, which are not inventive and may be made by persons skilled in the art after reading this description are made without departing from the spirit of the invention and within the scope of the appended claims.
Claims (10)
1. An adsorbent material for the removal of blood cytokines, characterized by: comprises an adsorption carrier, wherein the adsorption carrier is grafted with alkyl methacrylate, and the adsorption carrier is fixedly loaded with acetylated cysteine, acetylated glycyrrhizic acid or a combination of the acetylated cysteine and the acetylated glycyrrhizic acid.
2. The adsorbent material for removing blood cytokines according to claim 1, wherein: the adsorption carrier is one or two of polystyrene divinyl benzene microspheres and polymethyl methacrylate resin microspheres.
3. The adsorbent material for removing blood cytokines according to claim 1, wherein: the number of carbon atoms in the alkyl group of the alkyl methacrylate is twelve or more.
4. The adsorbent for removing blood cytokines according to claim 1, whereinCharacterized in that: the adsorption carrier is a polystyrene divinylbenzene microsphere, the aperture of the polystyrene divinylbenzene microsphere is 2 to 50nm, and the specific surface area is 500 to 1000m 2 /g。
5. The adsorbent material for removing blood cytokines according to claim 1, wherein: the adsorption carrier is fixedly loaded with the combination of acetylated cysteine and acetylated glycyrrhizic acid, and the weight ratio of the cysteine to the glycyrrhizic acid is 1 (0.2 to 3).
6. The adsorbent material for removing blood cytokines according to claim 1, wherein: the acetylating agent adopted by the acetylated cysteine and the acetylated glycyrrhizic acid is one or two of acetic acid and acetyl chloride.
7. The adsorbent material for removing blood cytokines according to claim 1, wherein: the adsorption carrier is also immobilized with one or more of polymyxin B sulfate, polylysine and polyethyleneimine.
8. The adsorbent material for removing blood cytokines according to claim 1 or 2, characterized in that: the adsorption carrier is connected to the amino connecting arm through a polyamine compound, and the adsorption carrier fixedly carries acetylated cysteine, acetylated glycyrrhizic acid or a combination of the acetylated cysteine and the acetylated glycyrrhizic acid through the amino connecting arm.
9. The adsorbent material for removing blood cytokines according to claim 8, wherein: and (3) before the adsorption carrier is connected to the amido connecting arm, carrying out epoxidation reaction.
10. The preparation method of the adsorbing material for removing the blood cytokines is characterized by comprising the following steps: the method comprises the following steps:
grafting alkyl methacrylate on the adsorption carrier, carrying out epoxidation reaction, carrying out amination reaction on the obtained epoxy product and a polyamine compound to form an amino connecting arm, carrying out condensation reaction on the amino connecting arm and cysteine and/or glycyrrhizic acid, and carrying out acetylation reaction on the cysteine and/or glycyrrhizic acid to prepare the adsorption material for removing the blood cell factors.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003275296A (en) * | 2002-03-20 | 2003-09-30 | Asahi Kasei Corp | Blood compatible material |
| CN103585977A (en) * | 2013-11-22 | 2014-02-19 | 珠海健帆生物科技股份有限公司 | Cytokine adsorbent for hemoperfusion and preparation method thereof |
| CN104525151A (en) * | 2014-12-02 | 2015-04-22 | 佛山市博新生物科技有限公司 | Endotoxin adsorbent used in hemoperfusion, and preparation method thereof |
| CN104959120A (en) * | 2015-06-19 | 2015-10-07 | 佛山市博新生物科技有限公司 | Inflammatory factor adsorbing agent for blood perfusion and preparation method |
| CN113613776A (en) * | 2019-03-29 | 2021-11-05 | 旭化成医疗株式会社 | Blood purifier |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003275296A (en) * | 2002-03-20 | 2003-09-30 | Asahi Kasei Corp | Blood compatible material |
| CN103585977A (en) * | 2013-11-22 | 2014-02-19 | 珠海健帆生物科技股份有限公司 | Cytokine adsorbent for hemoperfusion and preparation method thereof |
| CN104525151A (en) * | 2014-12-02 | 2015-04-22 | 佛山市博新生物科技有限公司 | Endotoxin adsorbent used in hemoperfusion, and preparation method thereof |
| CN104959120A (en) * | 2015-06-19 | 2015-10-07 | 佛山市博新生物科技有限公司 | Inflammatory factor adsorbing agent for blood perfusion and preparation method |
| CN113613776A (en) * | 2019-03-29 | 2021-11-05 | 旭化成医疗株式会社 | Blood purifier |
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