CN113797900B - Adsorption material for blood purification, preparation method and application thereof, adsorption column and blood adsorption device - Google Patents
Adsorption material for blood purification, preparation method and application thereof, adsorption column and blood adsorption device Download PDFInfo
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- CN113797900B CN113797900B CN202111149337.5A CN202111149337A CN113797900B CN 113797900 B CN113797900 B CN 113797900B CN 202111149337 A CN202111149337 A CN 202111149337A CN 113797900 B CN113797900 B CN 113797900B
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- hollow fiber
- adsorption
- blood
- chloride
- blood purification
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Classifications
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- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
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- D06M13/35—Heterocyclic compounds
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Abstract
The invention provides an adsorption material for purifying blood, which is formed by modifying organic sulfonyl chloride to form a grafted chain with sulfonyl ester groups on an EVOH hollow fiber matrix and then connecting the sulfonyl ester groups with amino compound ligands in a covalent bond manner; the preparation method of the adsorption material mainly comprises the steps of grafting activation and immobilization of amino compound ligand on the surface of EVOH hollow fiber. The adsorption material for blood purification is safe and efficient, can selectively adsorb various pathogenic factors, has high clearance rate, and has a simple preparation process.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to an adsorption material for purifying blood, a preparation method and application thereof, an adsorption column and a blood adsorption device.
Background
Bilirubin is a metabolite of heme in senescent red blood cells, and is normally removed from the body by further metabolism after the liver has been combined with glucuronic acid. When liver is dysfunctional, bilirubin metabolism is impaired, and is accumulated in blood, hyperbilirubinemia (hyperbilirubibinmia) occurs, and bilirubin encephalopathy jaundice or nuclear jaundice is further caused, and finally tissue cell necrosis, absentmindedness, paralysis or death may be caused. Blood perfusion (Hemoperfusion) is an effective method for treating hyperbilirubinemia, and various blood purification materials for removing bilirubin have been developed at present, but most of the blood purification materials are easier to remove free bilirubin in alkaline solution, and the removal effect on albumin-bound bilirubin is not ideal. Particularly in an actual human plasma environment, many other substances, including albumin, are adsorbed simultaneously with bilirubin due to the complexity of the plasma environment, resulting in nonspecific adsorption, and the adsorption capacity of the material for bilirubin is reduced.
Sepsis is a complex process of infection by a variety of microorganisms (bacteria, fungi, viruses, parasites, etc.) and systemic inflammatory responses. Infections at essentially any site can lead to sepsis such as pneumonia, enteritis, peritonitis, cholangitis, urinary system infections, cellulitis, meningitis, etc. Sepsis is a worldwide medical problem with high morbidity and mortality, and is a major cause of death in Intensive Care Units (ICU) patients. Among them, gram bacteria include gram-negative bacteria and gram-positive bacteria, most of which belong to the group of intestinal bacteria, which produce endotoxins that can induce sepsis; most of the suppurative cocci belong to gram-positive bacteria, which can produce exotoxins to cause diseases, and common gram-positive bacteria are: staphylococci, streptococci, pneumococci, bacillus anthracis, diphtheria bacillus, tetanus bacillus, and the like. Large scale epidemiological data have shown that in recent years there has been a significant increase in sepsis and septic shock caused by gram positive bacteria, which has now reached over 50% of sepsis incidence. Common complications of sepsis include shock, acute lung injury, acute respiratory distress syndrome, deep vein thrombosis, stress ulcers, metabolic acidosis, disseminated Intravascular Coagulation (DIC), and even multiple organ dysfunction.
The occurrence and exacerbation of many diseases are the result of accumulation of pathogenic factors in the body, so that the pathogenic factors are specifically and effectively removed from the body by a blood purification method, and meanwhile, the damage to the body is avoided, and the method is a problem continuously explored in clinical medicine for decades. Traditional hemodialysis or hemodiafiltration can only remove small molecules, and can not effectively remove macromolecular pathogenic substances, and blood perfusion is needed. And the coupling reagent used in the research of the traditional blood perfusion technology is generally cyanogen bromide, trichlorotriazine, carbonyl diimidazole, sodium periodate, epichlorohydrin and the like, wherein the cyanogen bromide is a highly toxic substance, the synthesis process has great harm to human bodies and the environment, and the ligand is coupled by a cyanogen bromide method and easily falls off into the human bodies, so that great side effects are generated for patients. In addition, the traditional method adopts epichlorohydrin and carbonyl diimidazole as coupling reagent to activate carrier for coupling PMB, and avoids using virulent substance cyanogen bromide, but the preparation process has more reaction steps, and the adsorption material can be synthesized only through five steps of chemical reactions, and the method is complex, so that the obtained adsorption material has large batch-to-batch difference and unstable performance. The endotoxin adsorption material is prepared by a traditional method, and is a polystyrene woven fiber with polymyxin B on the surface, and the technology route is used for easily causing residues of strong-irritation chemical substances chloromethyl ether which are strong carcinogens, so that great potential safety hazards exist.
Disclosure of Invention
Based on the above, the invention provides an adsorption material for blood purification, which is safe and efficient, can selectively adsorb various pathogenic factors, has higher clearance rate and simple preparation process.
The invention is realized by the following technical scheme.
An adsorbent material for blood purification, which is formed by modifying an organic sulfonyl chloride to form a graft chain having a sulfonyl ester group on an EVOH hollow fiber substrate, and then covalently linking the sulfonyl ester group with an amino compound ligand.
In one embodiment, the amino compound is selected from at least one of n-butylamine, polymyxin B sulfate, lysozyme, and kukoamine B.
In one embodiment, the organic sulfonyl chloride is selected from at least one of p-toluenesulfonyl chloride, 2-trifluoroethanesulfonyl chloride, p-nitrobenzenesulfonyl chloride, 2,4, 6-triisopropylbenzenesulfonyl chloride and phenylsulfonyl chloride.
In one embodiment, the EVOH hollow fiber matrix is a hollow fiber woven tube, a hollow fiber woven mesh, or a hollow fiber tubular nonwoven material; and/or
The EVOH hollow fiber matrix has an inner diameter of 200-300 [ mu ] m.
The invention also provides a preparation method of the adsorption material, which comprises the following steps:
mixing the EVOH hollow fiber matrix with the organic sulfonyl chloride, performing an activation reaction, and then mixing with the amino compound to perform a covalent coupling reaction.
In one embodiment, the temperature of the activation reaction is 20-30 ℃, and the time of the activation reaction is 1-3 hours; and/or
The solvent adopted in the activation reaction is an organic solvent; and/or
Mixing the EVOH hollow fiber matrix with the organic sulfonyl chloride and then mixing with pyridine; the mass ratio of the EVOH hollow fiber matrix to the organic sulfonyl chloride to the pyridine is (15-30) 1 (1-5); and/or
The amino compound is added in the form of a solution, and the concentration of the solution is 1 mg/mL-50 mg/mL.
In one embodiment, the conditions for the covalent coupling reaction are: the conditions of the covalent coupling reaction are: the temperature is 4-40 ℃, the time is 8-24 h, and the pH is 4.5-9.5; and/or
The covalent coupling reaction further comprises a capping step: and (3) soaking the substrate subjected to covalent coupling ligand reaction with tris (hydroxymethyl) aminomethane hydrochloride with the pH of 7.5-9.5 at 20-30 ℃ for reaction for 6-24 h, and closing redundant active groups on the substrate.
The invention also provides the use of an adsorbent material for blood purification as described above for the adsorption of biological components in blood for non-disease diagnostic and therapeutic purposes.
The present invention also provides an adsorption column comprising the adsorption material for blood purification as described above.
The present invention also provides a blood adsorbing device comprising the adsorbing material for blood purification as described above or the adsorbing column as described above.
Compared with the prior art, the adsorption material for purifying blood has the following beneficial effects:
according to the invention, the functional group sulfonyl ester group is introduced on the surface of the EVOH hollow fiber through the activation of organic sulfonyl chloride, and the EVOH hollow fiber can be coupled with a plurality of ligands containing amino groups, so that the EVOH hollow fiber has the function of selectively adsorbing a plurality of pathogenic factors, and the higher pathogenic factor clearance rate is achieved; in addition, the adsorption material for blood purification has good blood compatibility.
Furthermore, the adsorption material for blood purification is safe and nontoxic, has a simple preparation process, does not need to use strong-irritation chemical substances or extremely toxic substances, and is suitable for industrialization.
Detailed Description
In order that the invention may be readily understood, a more particular description of the invention will be rendered by reference to specific embodiments that are illustrated in the appended drawings. Preferred embodiments of the present invention are shown in the examples. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
An adsorption material for purifying blood is prepared through modifying the organic sulfonyl chloride to form grafted chain with sulfonyl ester group on the hollow EVOH fibre matrix, and covalent linking between sulfonyl ester group and amino compound ligand.
It is understood that in the present invention, EVOH is an ethylene-vinyl alcohol copolymer.
According to the invention, EVOH hollow fiber is screened out as a specific matrix, organic sulfonyl chloride is screened out to activate the EVOH hollow fiber, specific sulfonyl ester group is introduced to couple with amino compound ligand, the matrix, the coupling group and the ligand are mutually matched, the adsorption effect is synergistically improved, and compared with the traditional adsorption material, the adsorption effect of the finally obtained adsorption material on pathogenic components is obviously enhanced.
In the present invention, the amino compound binds to at least one pathogenic component in blood or plasma. More specifically, pathogenic components include bilirubin, endotoxin, sepsis pathogen molecules (endotoxin, peptidoglycan and DNA) or sepsis pathogen (gram positive bacteria, gram negative bacteria and fungi).
In a specific example, the amino compound is selected from at least one of n-butylamine, polymyxin B sulfate, lysozyme, and kukoamine B.
In a specific example, the organic sulfonyl chloride is selected from at least one of p-toluenesulfonyl chloride, 2-trifluoroethanesulfonyl chloride, p-nitrobenzenesulfonyl chloride, 2,4, 6-triisopropylbenzenesulfonyl chloride and benzenesulfonyl chloride.
In a specific example, the EVOH hollow fiber matrix is a hollow fiber woven tube, a hollow fiber woven mesh, or a hollow fiber tubular nonwoven material.
The hollow fiber woven tube is a tubular material woven by hollow fibers, the hollow fiber woven net is a net-shaped material woven by hollow fibers, and the hollow fiber tubular nonwoven material can be a short hollow fiber tubular nonwoven material or a long hollow fiber tubular nonwoven material, wherein the short hollow fiber tubular nonwoven material is a tubular material formed by cutting long hollow fibers into short hollow fibers without any weaving.
In a specific example, the EVOH hollow fiber matrix has an inner diameter of 200 μm to 300. Mu.m. It is understood that in the present invention, the inner diameter of the EVOH hollow fiber matrix includes, but is not limited to, 200 μm, 210 μm, 220 μm, 230 μm, 240 μm, 250 μm, 260 μm, 270 μm, 280 μm, 290 μm, 300 μm.
The invention also provides a preparation method of the adsorption material for purifying blood, which comprises the following steps:
mixing EVOH hollow fiber matrix with organic sulfonyl chloride, activating, mixing with amino compound, and covalent coupling reaction.
In the invention, functional group sulfonyl ester groups are introduced on the surface of an EVOH hollow fiber matrix through activation of organic sulfonyl chloride, and nucleophilic groups of amino compounds are amino-substituted sulfonyl groups during covalent coupling.
In a specific example, the temperature of the activation reaction is 20℃to 30 ℃. It is understood that in the present invention, the temperature of the activation reaction includes, but is not limited to, 20 ℃, 21 ℃, 22 ℃, 23 ℃, 24 ℃,25 ℃, 26 ℃, 27 ℃, 28 ℃, 29 ℃, 30 ℃.
In a specific example, the time of the activation reaction is 1 to 3 hours. It is understood that in the present invention, the time of the activation reaction includes, but is not limited to, 1h, 1.5h, 2h, 2.5h, 3h.
In a specific example, the solvent employed in the activation reaction is an organic solvent. More specifically, the solvent used in the activation reaction is an anhydrous, active hydrogen-free organic phase. Preferably, the solvent used in the activation reaction is acetone.
In a specific example, the EVOH hollow fiber matrix is mixed with the organic sulfonyl chloride and then with pyridine; the mass ratio of the EVOH hollow fiber matrix to the organic sulfonyl chloride to the pyridine is (15-30) 1 (1-5).
It is understood that in the present invention, the mass ratio of EVOH hollow fiber matrix, organic sulfonyl chloride to pyridine includes, but is not limited to: 15:1:1, 20:1:1, 25:1:1, 30:1:1, 15:1:2, 20:1:2, 25:1:2, 30:1:2, 15:1:3, 20:1:3, 25:1:3, 30:1:3, 15:1:4, 20:1:4, 25:1:4, 30:1:4, 15:1:5, 20:1:5, 25:1:5, 30:1:5.
In a specific example, the amino compound is added as a solution, and the concentration of the solution is 1mg/mL to 50mg/mL. It will be appreciated that in the present invention, the concentration of the amino compound includes, but is not limited to, 1mg/mL, 5mg/mL, 10mg/mL, 15mg/mL, 20mg/mL, 25mg/mL, 30mg/mL, 35mg/mL, 40mg/mL, 45mg/mL, 50mg/mL.
In a specific example, the temperature of the covalent coupling reaction is from 4 ℃ to 40 ℃. It is understood that in the present invention, the temperature of the covalent coupling reaction includes, but is not limited to, 4 ℃, 10 ℃, 15 ℃, 20 ℃,25 ℃, 30 ℃, 35 ℃, 40 ℃.
In a specific example, the time of the covalent coupling reaction is 8h to 24h. It is understood that in the present invention, the time of the covalent coupling reaction includes, but is not limited to, 8h, 9h, 10h, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h, 19h, 20h, 21h, 22h, 23h, 24h.
In a specific example, the pH of the covalent coupling reaction is between 4.5 and 9.5. It is understood that in the present invention, the pH of the covalent coupling reaction includes, but is not limited to, 4.5, 5.5, 6.5, 7.5, 8.5, 9.5.
In a specific example, the covalent coupling reaction is followed by a capping step: and (3) soaking the substrate subjected to covalent coupling reaction with tris hydrochloride to perform reaction, and blocking redundant active groups on the substrate.
In a specific example, the pH of the tris hydrochloride is 7.5 to 9.5. It is understood that in the present invention, the pH of the tris hydrochloride includes, but is not limited to, 7.5, 8, 8.5, 9, 9.5.
In a specific example, the soaking reaction temperature is 20 ℃ to 30 ℃. It is understood that in the present invention, the temperature of the soaking reaction includes, but is not limited to, 20 ℃, 21 ℃, 22 ℃, 23 ℃, 24 ℃,25 ℃, 26 ℃, 27 ℃, 28 ℃, 29 ℃, 30 ℃.
In a specific example, the soaking reaction time is 6-24 hours. It is understood that in the invention, the time of the soaking reaction includes, but is not limited to, 6h, 8h, 10h, 12h, 13h, 14h, 15h, 16h, 18h, 20h, 22h, 24h.
In a more specific example, the method for preparing the adsorption material includes the following steps:
mixing EVOH hollow fiber matrix, organic sulfonyl chloride and pyridine in the mass ratio of (15-30) to 1 (1-5), and performing an activation reaction at 20-30 ℃ for 1-3 h;
then adding the mixture into 1 mg/mL-50 mg/mL of amino compound solution, adjusting the pH to 4.5-9.5, and soaking the mixture at the temperature of 4-30 ℃ for covalent coupling reaction for 8-24 h;
and (3) soaking the product of the covalent coupling reaction with tris (hydroxymethyl) aminomethane hydrochloride with the pH of 7.5-9.5 at 20-30 ℃ for reaction for 6-24 hours, and sealing redundant active groups on the matrix.
The invention also provides the application of the adsorption material for purifying blood in adsorbing biological components in blood for non-disease diagnosis and treatment.
It is understood that biological components include, but are not limited to, bilirubin, endotoxins, sepsis pathogen molecules (endotoxins, peptidoglycans, and DNA) or sepsis pathogens (gram positive bacteria, gram negative bacteria, and fungi).
The invention also provides an adsorption column containing the adsorption material for blood purification.
The invention also provides a blood adsorption device comprising the adsorption material for blood purification or the adsorption column.
The adsorbent for blood purification and the method of preparing the same according to the present invention will be described in further detail with reference to specific examples. The raw materials used in the following examples are all commercially available products unless otherwise specified.
Example 1
The embodiment provides a bilirubin adsorption material with n-butylamine as a ligand, which comprises the following specific steps:
100g of dry EVOH hollow fiber (tubular, 200 μm inner diameter), 5g of p-toluenesulfonyl chloride (dissolved in 100mL of acetone) and 10g of pyridine were placed in a vessel, immersed at 25℃for 1.5 hours, taken out, washed with 1L of acetone, and the ratio of the two was 30: 70. 50: 50. 70:30 of 1mmol/L of hydrochloric acid-acetone mixture, each substrate was washed 2 times, and finally washed with 1mmol/L of hydrochloric acid to give a tosylated substrate, which was stored in 1mmol/L of HCl at 4℃for several weeks without losing coupling efficiency and was labeled B0.
5g of the prepared B0 is placed in 0.15M boric acid buffer solution containing 15mg/mL of n-butylamine, the pH value is 8.2, the soaking reaction is carried out for 24 hours at 25 ℃, the washing is carried out by using 20 times of deionized water, the soaking reaction is carried out for 12 hours at 25 ℃ by using 8.0-0.1 mol/L Tris-HCl, redundant active groups on the matrix are blocked, and finally the matrix is fully washed by using 1.0mol/L NaCl and water, so that the bilirubin adsorption material marked as B1 is obtained.
Example 2
The embodiment provides an endotoxin adsorption material using polymyxin B sulfate as a ligand, which is specifically as follows:
100g (tubular, 200 μm inner diameter) of dry EVOH hollow fiber, 5g of p-toluenesulfonyl chloride (dissolved in 100mL of acetone) and 10g of pyridine were placed in a vessel, and the reaction was immersed for 1.5 hours, taken out, washed with 1L of acetone, and then washed with water in a ratio of 30: 70. 50: 50. 70:30 of 1mmol/L of hydrochloric acid-acetone mixture, each substrate was washed 2 times, and finally washed with 1mmol/L of hydrochloric acid to give a tosylated substrate, which was stored in 1mmol/L of HCl at 4℃for several weeks without losing coupling efficiency and was labeled B0.
5g of the prepared B0 is placed in a solution containing 50mg/mL PMB (dissolved by PBS with pH 7.4), soaked and reacted for 24 hours at 25 ℃, then washed by deionized water with 20 times of volume, soaked and reacted for 12 hours at 25 ℃ by pH 8.0 and 0.1mol/LTris-HCl, redundant active groups on the matrix are blocked, and finally the matrix is fully washed by 1.0mol/L NaCl and water, so that an endotoxin adsorbing material is obtained and marked as B2.
Example 3
The embodiment provides a sepsis pathogenic bacteria adsorbing material with lysozyme as a ligand, which is specifically as follows:
100g (tubular, 200 μm inner diameter) of dry EVOH hollow fiber, 5g of p-toluenesulfonyl chloride (dissolved in 100mL of acetone) and 10g of pyridine were placed in a vessel, and the reaction was immersed for 1.5 hours, taken out, washed with 1L of acetone, and then washed with water in a ratio of 30: 70. 50: 50. 70:30 of 1mmol/L of hydrochloric acid-acetone mixture, each substrate was washed 2 times, and finally washed with 1mmol/L of hydrochloric acid to give a tosylated substrate, which was stored in 1mmol/L of HCl at 4℃for several weeks without losing coupling efficiency and was labeled B0.
5g of the prepared B0 is placed in 0.2M phosphate buffer solution with pH7.4 containing 20mg/mL lysozyme, soaked and reacted for 24 hours at 25 ℃, then washed by deionized water with the volume of 20 times, soaked and reacted for 12 hours at 25 ℃ by Tris-HCl with the pH of 8.0 and 0.1mol/L, redundant active groups on the matrix are closed, finally the matrix is fully washed by NaCl with the concentration of 1.0mol/L and water, and the sepsis pathogenic bacteria adsorbing material is marked as B3.
Example 4
The embodiment provides a sepsis pathogen molecule adsorption material with kukoamine B as a ligand, which comprises the following specific steps:
100g (tubular, 200 μm inner diameter) of dry EVOH hollow fiber, 5g of p-toluenesulfonyl chloride (dissolved in 100mL of acetone) and 10g of pyridine were placed in a vessel, and the reaction was immersed for 1.5 hours, taken out, washed with 1L of acetone, and then washed with water in a ratio of 30: 70. 50: 50. 70:30 of 1mmol/L of hydrochloric acid-acetone mixture, each substrate was washed 2 times, and finally washed with 1mmol/L of hydrochloric acid to give a tosylated substrate, which was stored in 1mmol/L of HCl at 4℃for several weeks without losing coupling efficiency and was labeled B0.
5g of B0 prepared by the method is placed in 0.2M phosphate buffer solution with pH7.4 containing 5mg/mL of kukoamine B, soaked at 25 ℃ for 24 hours, washed by 20 times of deionized water, soaked at 25 ℃ for 12 hours by using pH 8.0 and 0.1mol/L Tris-HCl, redundant active groups on the matrix are blocked, and finally the matrix is fully washed by using 1.0mol/LNaCl and water, so that the sepsis pathogenic bacteria adsorbing material is marked as B4.
Example 5
The embodiment provides an endotoxin adsorption material using polymyxin B sulfate as a ligand, which is specifically as follows:
100g (tubular, 200 μm inner diameter) of dry EVOH hollow fiber, 5g of 2, 2-trifluoroethanesulfonyl chloride (dissolved in 100mL of acetone) and 10g of pyridine were placed in a vessel, immersed and reacted for 1.5 hours, taken out, washed with 1L of acetone, and then mixed with a ratio of 30: 70. 50: 50. 70:30 of 1mmol/L of a mixture of hydrochloric acid and acetone, each of which was washed 2 times, was finally washed with 1mmol/L of hydrochloric acid to give a 2, 2-trifluoroethanesulfonylated substrate which was stored in 1mmol/L of HCl at 4℃for several weeks without losing the coupling efficiency and was designated as B5.
5g of the prepared B0 is placed in a solution containing 50mg/mL PMB (dissolved by PBS with pH 7.4), soaked for 24 hours at 4 ℃, washed by deionized water with 20 times of volume, soaked for 12 hours at 25 ℃ by pH 7.0 and 0.1mol/LTris-HCl, redundant active groups on the matrix are blocked, and finally the matrix is fully washed by 1.0mol/L NaCl and water, so that an endotoxin adsorbing material marked as B5' is obtained.
Comparative example 1
The comparative example provides an endotoxin adsorption material using polymyxin B sulfate as a ligand, which is specifically as follows:
100g of dried agarose gel, 5g of p-toluenesulfonyl chloride (dissolved in 100mL of acetone) and 10g of pyridine are placed in a container for soaking reaction for 1.5h, taken out, washed with 1L of acetone and then washed with water according to the ratio of 30: 70. 50: 50. 70:30 of 1mmol/L of hydrochloric acid-acetone mixture, each substrate was washed 2 times, and finally washed with 1mmol/L of hydrochloric acid to give a tosylated substrate, which was stored at 4℃in 1mmol/LHCl for several weeks without losing coupling efficiency and was marked C0.
5g of the prepared C0 is placed in a solution containing 50mg/mL PMB (dissolved by PBS with pH 7.4), soaked for 24 hours at 25 ℃, washed by deionized water with 20 times of volume, soaked for 12 hours at 25 ℃ by pH 8.0 and 0.1mol/LTris-HCl, redundant active groups on the matrix are blocked, and finally the matrix is fully washed by 1.0mol/L NaCl and water, so that an endotoxin adsorbing material marked as C1 is obtained.
Comparative example 2
The comparative example provides a bilirubin adsorption material with n-butylamine as ligand, which comprises the following specific steps:
100g of dry PVA, 5g of p-toluenesulfonyl chloride (dissolved in 100mL of acetone) and 10g of pyridine were placed in a vessel, soaked for 1.5h, taken out, washed with 1L of acetone, and re-used in a ratio of 30: 70. 50: 50. 70:30 of 1mmol/L of hydrochloric acid-acetone mixture, each substrate was washed 2 times, and finally washed with 1mmol/L of hydrochloric acid to give a tosylated substrate, which was stored in 1mmol/L of HCl at 4℃for several weeks without losing coupling efficiency, and was designated as D0.
5g of the prepared D0 is placed in a solution containing 50mg/mL PMB (dissolved by PBS with pH 7.4), soaked for 24 hours at 25 ℃, washed by deionized water with 20 times of volume, soaked for 12 hours at 25 ℃ by pH 8.0 and 0.1mol/LTris-HCl, redundant active groups on the matrix are blocked, and finally the matrix is fully washed by 1.0mol/L NaCl and water, so that an endotoxin adsorbing material marked as D1 is obtained.
Comparative example 3
The comparative example provides a bilirubin adsorption material with n-butylamine as ligand, which comprises the following specific steps:
100g of dry EVOH hollow fiber (tubular, inner diameter 200 μm), 6g of epichlorohydrin and 10g of pyridine were placed in a vessel, and the vessel was immersed for 1.5 hours, taken out, washed with 1L of acetone, and the ratio of the reaction solution to the acetone was 30: 70. 50: 50. 70:30 of 1mmol/L of hydrochloric acid-acetone mixture, each substrate was washed 2 times, and finally washed with 1mmol/L of hydrochloric acid to give a modified substrate, which was stored in 1mmol/L of HCl at 4℃for several weeks without losing coupling efficiency and was labeled E0.
5g of E0 prepared by the method is placed in a solution containing 50mg/mL PMB (dissolved by PBS with pH 7.4), soaked for 24 hours at 25 ℃, washed by deionized water with 20 times of volume, soaked for 12 hours at 25 ℃ by pH 8.0 and 0.1mol/LTris-HCl, redundant active groups on the matrix are blocked, and finally the matrix is fully washed by 1.0mol/L NaCl and water, so that an endotoxin adsorbing material marked as E1 is obtained.
Effect verification test-adsorption Performance test
The adsorption performance of the adsorption materials prepared in the above examples 1 to 5 and comparative examples 1 to 3 was tested as follows:
adsorption bilirubin assay: washing the prepared bilirubin adsorption material with a large amount of water, draining to constant weight, weighing 3g, and packagingThe column was then pre-filled with physiological saline, and 30mL of bovine plasma to which bilirubin had been added was added, followed by dynamic adsorption cycling for 2h, and the bilirubin levels in the bovine plasma before and after adsorption were tested.
Adsorption endotoxin experiment: the prepared endotoxin adsorption material is washed by a large amount of water, pumped to constant weight for standby,the column was soaked with 1M sodium hydroxide overnight and washed with pyrogen-free water, then 3g was weighed, put into the column washed with the above-mentioned alkali, then pre-filled with physiological saline, then added into 30mL of bovine plasma to which endotoxin had been added, and the dynamic adsorption was circulated for 2 hours, and the endotoxin content in the bovine plasma before and after adsorption was tested.
Adsorption of sepsis pathogen experiments: the prepared endotoxin adsorption material is washed by a large amount of water, pumped to constant weight for standby,the column was soaked with 1M sodium hydroxide overnight and washed with pyrogen-free water, then 3g was weighed and placed into the column after washing with the above-mentioned alkali, then pre-filled with physiological saline, and then 30mL of bovine plasma to which E.coli (E.coli), staphylococcus aureus (S.aureus) and Candida albicans (C.albicans) had been added was added, and the dynamic adsorption was circulated for 2 hours, and the sepsis pathogenic bacteria content in the bovine plasma before and after adsorption was tested.
Adsorption of sepsis pathogen molecules experiments: the prepared endotoxin adsorption material is washed by a large amount of water, pumped to constant weight for standby,soaking the column in 1M sodium hydroxide overnight, cleaning with pyrogen-free water, weighing 3g, and packagingAnd (3) putting the mixture into the column after the alkali soaking washing, then pre-filling the column with normal saline, adding the pretreated column into 30mL of bovine plasma with added endotoxin, peptidoglycan, DNA and IL-6, dynamically adsorbing and circulating for 2h, and testing the content of the endotoxin, peptidoglycan, DNA and IL-6 in the bovine plasma before and after the adsorption.
The multi-adaptability and the considerable efficacy results of the adsorption materials prepared in examples 1 to 5 and comparative examples 1 to 3 for selectively adsorbing different components from whole blood or plasma are shown in table 1.
TABLE 1
Note that: the organic sulfonyl chloride method in B5' is 2, 2-trifluoro ethane sulfonyl chloride, and the rest is p-toluene sulfonyl chloride
Effect verification test two blood compatibility test
The adsorption materials prepared in examples 1 to 5 and comparative examples 1 to 3 were subjected to blood compatibility test, and the specific procedures are as follows:
hemolysis experiment: the hemolysis experiment was performed according to GB/T16886.4-2003 medical instrument biological evaluation part 4 and blood interaction test selection and GB/T16175-2008 medical organosilicon Material biological evaluation test method. 1g of the adsorption material prepared in the examples 2-5 is added into each tube of the sample group, and 10ml of sodium chloride injection is added; adding 10ml of sodium chloride injection into each tube of the negative control group; distilled water was added 10ml per tube for the positive control group. Each group operated 3 tubes in parallel. Placing all test tubes into a constant temperature water bath (37+ -1) deg.C, maintaining for 30min, adding 0.2ml diluted rabbit blood into each test tube, mixing gently, and maintaining in the water bath (37+ -1) deg.C for 60min. The liquid in the pouring tube was centrifuged at 800g for 5min. The supernatant was pipetted into a cuvette and absorbance was measured with a spectrophotometer at 545nm wavelength. The absorbance of the sample combination control group was averaged over 3 tubes. The absorbance of the negative control should be no greater than 0.03, the absorbance of the positive control should be 0.8.+ -. 0.3, otherwise the test should be repeated. Hemolysis ratio = (a-B)/(C-B) ×100%, where a is the sample group absorbance; b is the absorbance of the negative control group; c is the absorbance of the positive control group.
Blood compatibility experiments: 1g of each of the adsorption materials prepared in examples 1 to 5 and comparative examples 1 to 3 was taken, immersed in physiological saline for 10 hours, then packed into a column, 10mL of anticoagulated rabbit whole blood with heparin sodium was injected by a syringe, adsorbed for 2 hours at a flow rate of 20mL/min, and a control experiment was performed while adding a hollow column. The changes in the blood components before and after adsorption were measured by a Beckman LH750 hemocyte analyzer.
The results show that: (1) The hemolysis rate of the adsorption materials prepared in the examples 1-5 and the comparative examples 1-3 is less than 2%, and is lower than 5% required by the national standard. (2) The adsorption materials prepared in examples 1-5 and comparative examples 1-3 showed little change in the main components in the blood before and after adsorption, and the percentage of decrease was within 5%. The above results show that the adsorption materials prepared by the invention have good blood compatibility.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples merely represent a few embodiments of the present invention, which facilitate a specific and detailed understanding of the technical solutions of the present invention, but are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. It should be understood that, based on the technical solutions provided by the present invention, those skilled in the art may obtain technical solutions through logical analysis, reasoning or limited experiments, which are all within the scope of protection of the appended claims. The scope of the patent of the invention should therefore be determined with reference to the appended claims, which are to be construed as in accordance with the doctrines of claim interpretation.
Claims (8)
1. An adsorption material for blood purification, characterized in that the adsorption material is formed by modifying an organic sulfonyl chloride to form a graft chain with a sulfonyl ester group on an EVOH hollow fiber substrate and then covalently connecting the sulfonyl ester group with an amino compound ligand;
the amino compound is at least one of polymyxin B sulfate, lysozyme and kukoamine B;
the EVOH hollow fiber matrix is a hollow fiber woven tube, a hollow fiber woven net or a hollow fiber tubular nonwoven material, and the inner diameter of the EVOH hollow fiber matrix is 200-300 mu m.
2. The absorbent for blood purification according to claim 1, wherein the organic sulfonyl chloride is at least one selected from the group consisting of p-toluenesulfonyl chloride, 2-trifluoroethanesulfonyl chloride, p-nitrobenzenesulfonyl chloride, 2,4, 6-triisopropylbenzenesulfonyl chloride and phenylsulfonyl chloride.
3. The method for producing an adsorbent material for blood purification according to claim 1 or 2, characterized by comprising the steps of:
mixing the EVOH hollow fiber matrix with the organic sulfonyl chloride, performing an activation reaction, and then mixing with the amino compound to perform a covalent coupling reaction.
4. The method for producing an adsorbent for blood purification according to claim 3, wherein the temperature of the activation reaction is 20 to 30℃and the time of the activation reaction is 1 to 3 hours; and/or
The solvent adopted in the activation reaction is an organic solvent; and/or
Mixing the EVOH hollow fiber matrix with the organic sulfonyl chloride and then mixing with pyridine; the mass ratio of the EVOH hollow fiber matrix to the organic sulfonyl chloride to the pyridine is (15-30) 1 (1-5); and/or
The amino compound is added in the form of a solution, and the concentration of the solution is 1 mg/mL-50 mg/mL.
5. The method for preparing an adsorbent material for blood purification according to claim 3 or 4, wherein the covalent coupling reaction conditions are: the temperature is 4-40 ℃, the time is 8-24 h, and the pH is 4.5-9.5; and/or
The covalent coupling reaction further comprises a capping step: and (3) soaking the substrate subjected to covalent coupling ligand reaction with tris (hydroxymethyl) aminomethane hydrochloride with the pH of 7.5-9.5 at 20-30 ℃ for reaction for 6-24 h, and closing redundant active groups on the substrate.
6. Use of the adsorbent material for blood purification according to claim 1 or 2 for the adsorption of biological components in blood for non-disease diagnosis and treatment purposes.
7. An adsorption column comprising the adsorption material for blood purification according to claim 1 or 2.
8. A blood adsorbing device comprising the adsorbing material for blood purification as claimed in claim 1 or 2 or the adsorption column as claimed in claim 7.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005021510A (en) * | 2003-07-04 | 2005-01-27 | Toyobo Co Ltd | Highly permeabile hollow fiber type hemocatharsis device |
| CN1583245A (en) * | 2004-05-25 | 2005-02-23 | 浙江科锐生物科技有限公司 | Endotoxin adsorptive material, preparing and use thereof |
| CN1876226A (en) * | 2006-01-27 | 2006-12-13 | 大连理工大学 | Bilirubin adsorption material for treating hyperbilirubinemia |
| CN101185880A (en) * | 2007-08-22 | 2008-05-28 | 大连理工大学 | Blood purification adsorption agent for clearing immune body and preparation method thereof |
| CN103769060A (en) * | 2014-01-23 | 2014-05-07 | 郑玥 | Adsorbent for removing bacterial endotoxin, DNA and peptidoglycan and preparation method and use |
| DE102015011884A1 (en) * | 2015-09-10 | 2017-03-16 | Sartorius Stedim Biotech Gmbh | Adsorption medium, process for its preparation, and use thereof for the purification of biomolecules |
| CN107486176A (en) * | 2017-09-11 | 2017-12-19 | 广州康盛生物科技有限公司 | A kind of sorbing material for blood purification and preparation method thereof |
| WO2019081688A1 (en) * | 2017-10-25 | 2019-05-02 | Nonwovens Innovation And Research Institute | Porous fibrous separation material |
| CN110508263A (en) * | 2019-08-22 | 2019-11-29 | 广州康盛生物科技有限公司 | A kind of adsorbent material and preparation method thereof for blood purification |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040054104A1 (en) * | 2002-09-05 | 2004-03-18 | Pacetti Stephen D. | Coatings for drug delivery devices comprising modified poly(ethylene-co-vinyl alcohol) |
-
2021
- 2021-09-29 CN CN202111149337.5A patent/CN113797900B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005021510A (en) * | 2003-07-04 | 2005-01-27 | Toyobo Co Ltd | Highly permeabile hollow fiber type hemocatharsis device |
| CN1583245A (en) * | 2004-05-25 | 2005-02-23 | 浙江科锐生物科技有限公司 | Endotoxin adsorptive material, preparing and use thereof |
| CN1876226A (en) * | 2006-01-27 | 2006-12-13 | 大连理工大学 | Bilirubin adsorption material for treating hyperbilirubinemia |
| CN101185880A (en) * | 2007-08-22 | 2008-05-28 | 大连理工大学 | Blood purification adsorption agent for clearing immune body and preparation method thereof |
| CN103769060A (en) * | 2014-01-23 | 2014-05-07 | 郑玥 | Adsorbent for removing bacterial endotoxin, DNA and peptidoglycan and preparation method and use |
| DE102015011884A1 (en) * | 2015-09-10 | 2017-03-16 | Sartorius Stedim Biotech Gmbh | Adsorption medium, process for its preparation, and use thereof for the purification of biomolecules |
| CN107486176A (en) * | 2017-09-11 | 2017-12-19 | 广州康盛生物科技有限公司 | A kind of sorbing material for blood purification and preparation method thereof |
| WO2019081688A1 (en) * | 2017-10-25 | 2019-05-02 | Nonwovens Innovation And Research Institute | Porous fibrous separation material |
| CN110508263A (en) * | 2019-08-22 | 2019-11-29 | 广州康盛生物科技有限公司 | A kind of adsorbent material and preparation method thereof for blood purification |
Non-Patent Citations (3)
| Title |
|---|
| 吴梧桐.《生物制药工艺学》.中国医药科技出版社,2015,第252-253页. * |
| 新型吸附膜及其血液净化应用研究;李佳文;《中国优秀硕士学位论文数据库 工程科技Ⅰ辑》;摘要、第20-21页，第27-41页 * |
| 蒋中华等.《生物分子固定化技术及应用》.化学工业出版社,1998,第49-51页. * |
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