CN110117379B - Adsorbing material for removing LDL (low density lipoprotein) in blood perfusion and preparation method thereof - Google Patents
Adsorbing material for removing LDL (low density lipoprotein) in blood perfusion and preparation method thereof Download PDFInfo
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- CN110117379B CN110117379B CN201810111001.1A CN201810111001A CN110117379B CN 110117379 B CN110117379 B CN 110117379B CN 201810111001 A CN201810111001 A CN 201810111001A CN 110117379 B CN110117379 B CN 110117379B
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- divinylbenzene
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- 230000008081 blood perfusion Effects 0.000 title claims abstract description 15
- 239000000463 material Substances 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 title abstract description 11
- 108010007622 LDL Lipoproteins Proteins 0.000 title abstract description 11
- 239000011347 resin Substances 0.000 claims abstract description 21
- 229920005989 resin Polymers 0.000 claims abstract description 21
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims abstract description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 7
- 239000004088 foaming agent Substances 0.000 claims abstract description 7
- 229920000669 heparin Polymers 0.000 claims abstract description 7
- 239000004584 polyacrylic acid Substances 0.000 claims abstract description 7
- 229940057995 liquid paraffin Drugs 0.000 claims abstract description 6
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims abstract description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 5
- 108010010803 Gelatin Proteins 0.000 claims abstract description 5
- 239000008273 gelatin Substances 0.000 claims abstract description 5
- 229920000159 gelatin Polymers 0.000 claims abstract description 5
- 235000019322 gelatine Nutrition 0.000 claims abstract description 5
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 5
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000002270 dispersing agent Substances 0.000 claims abstract description 4
- 229960002897 heparin Drugs 0.000 claims abstract description 4
- 239000004342 Benzoyl peroxide Substances 0.000 claims abstract description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims abstract description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 claims abstract description 3
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 3
- 239000000178 monomer Substances 0.000 claims abstract description 3
- 239000000499 gel Substances 0.000 claims abstract 2
- 239000003999 initiator Substances 0.000 claims abstract 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 32
- 239000004005 microsphere Substances 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 claims description 2
- HXHCOXPZCUFAJI-UHFFFAOYSA-N prop-2-enoic acid;styrene Chemical compound OC(=O)C=C.C=CC1=CC=CC=C1 HXHCOXPZCUFAJI-UHFFFAOYSA-N 0.000 claims description 2
- 235000019441 ethanol Nutrition 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 abstract description 9
- 239000003463 adsorbent Substances 0.000 abstract description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 230000010100 anticoagulation Effects 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229910000861 Mg alloy Inorganic materials 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- GJMMXPXHXFHBPK-UHFFFAOYSA-N [P].[Cl] Chemical compound [P].[Cl] GJMMXPXHXFHBPK-UHFFFAOYSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- XVBISOTZCMGTDI-UHFFFAOYSA-H calcium magnesium potassium sodium tricarbonate Chemical compound C([O-])([O-])=O.[Na+].[K+].[Mg+2].[Ca+2].C([O-])([O-])=O.C([O-])([O-])=O XVBISOTZCMGTDI-UHFFFAOYSA-H 0.000 description 1
- 238000009924 canning Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005485 electric heating Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003361 porogen Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3687—Chemical treatment
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/44—Polymerisation in the presence of compounding ingredients, e.g. plasticisers, dyestuffs, fillers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/04—Acids; Metal salts or ammonium salts thereof
- C08F220/06—Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
- C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
- C08J9/286—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum the liquid phase being a solvent for the monomers but not for the resulting macromolecular composition, i.e. macroporous or macroreticular polymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2387/00—Characterised by the use of unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Vascular Medicine (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Anesthesiology (AREA)
- Materials Engineering (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- External Artificial Organs (AREA)
Abstract
The invention relates to a macroporous adsorbent resin adsorbent which is high in safety, ideal in effectiveness, stable in structural performance and good in specific adsorption selectivity, and the macroporous adsorbent is coated and filled in a blood perfusion device tank body, so that low-density lipoprotein in blood is removed through a blood perfusion (HP) therapy. The resin adsorption material is synthesized by the following steps: preparing gel type pre-crosslinked polyacrylic acid divinylbenzene spheres by using acrylic acid and divinylbenzene as monomers, glycerol as a crosslinking agent, benzoyl peroxide as an initiator, liquid paraffin as a pore-foaming agent, gelatin as a dispersing agent and anhydrous aluminum trichloride as a catalyst; then heparin is used for modifying the polyacrylic divinyl benzene spheres so as to improve the anticoagulation property, the hydrophilicity and the biocompatibility of the resin.
Description
Technical Field
The invention belongs to the field of biomedical engineering, and particularly relates to a resin attached material for removing LDL through blood perfusion and a preparation method thereof.
Background
According to conservative statistics in 2012, more than 2 hundred million hypertension patients and more than 9000 ten thousand diabetes patients in China currently die of cardiovascular and cerebrovascular diseases every year by 200 ten thousand. By the end of 2015, chronic kidney disease patients in China are more as many as 1.3 hundred million people. The products in the field of domestic blood purification are fewer, and especially the products for blood perfusion with higher symptomatic low-density lipoprotein are fewer and fewer; at present, four or five companies for producing the blood perfusion device are mainly used in China, the annual total sales is about 10 million yuan, and the demand is increased along with the increasing requirements of people on the life quality, so that the product has a better market prospect, and once the product is put into the market, the product is expected to bring greater economic benefit.
With the development of the blood perfusion apparatus industry, the purification mode of blood perfusion has been accepted by medical experts at home and abroad, and with the development of scientific technology, some new technologies, new materials and new therapies continuously appear, and the application field and the indications of the blood perfusion apparatus are continuously expanded. With the development of national economy, the level of medical equipment is improved, the social medical security system is continuously established, hospitals above the ground level are basically equipped with dialysis machines, blood purification rooms are owned, the equipment rate of artificial kidney machines of some hospitals above the provincial and county levels reaches more than 70%, and in some regions of China, some blood perfusion apparatus products are brought into the range of medical insurance, which lays a material important foundation for the development of blood perfusion.
Disclosure of Invention
The patent aims to develop a novel adsorbent in a resin adsorption column, which is mainly used for treating low-density lipoprotein high caused by coronary heart disease, nephrotic syndrome, chronic renal failure, liver disease, diabetes, hyperlipidemia, obesity or strenuous exercise, and adsorbing excessive total cholesterol, triglyceride, low-density lipoprotein and the like in a patient body.
The technical scheme is as follows:
mixing acrylic acid and a divinylbenzene monomer, adding the mixture into an aqueous solution containing a gelatin dispersant and a liquid paraffin pore-foaming agent, adding a glycerol cross-linking agent at the same time, and reacting to obtain pre-crosslinked white polyacrylic acid styrene microspheres;
step two, heparin is adopted to heparinize the pre-crosslinked polyacrylic acid styrene microspheres to obtain heparinized acrylic acid styrene microspheres;
and step three, purifying the polyacrylic acid styrene microspheres by using petroleum ether and removing a pore-forming agent to obtain a cleaner final resin without chloromethyl ether and the like.
The present invention will be described in further detail with reference to specific embodiments. It is to be understood that the embodiments of the present invention are merely for illustrating the present invention and not for limiting the present invention, and that various substitutions and alterations made according to the common knowledge and conventional means in the art without departing from the technical idea of the present invention are included in the scope of the present invention.
The method comprises the following steps: synthesis of polyacrylic styrene microspheres (bench test):
TABLE 1 list of reagents required for the synthesis of polyacrylic acid styrene microspheres
The method comprises the following specific operations:
adding 500mL of purified water into a 1000mL three-neck flask (provided with a stirrer, a reflux pipe and a thermometer), adding 30g of gelatin dispersant, heating to 45-50 ℃, and stirring for dissolving to form a stable water dispersion phase; fully stirring and mixing acrylic acid, divinylbenzene, glycerol, benzoyl peroxide, pore-forming agent, liquid paraffin and anhydrous aluminum chloride to form a mixed oil phase, adding the mixed oil phase into the water dispersion phase, continuously stirring and heating to 80 ℃, carrying out polymerization crosslinking reaction for 4 hours, then continuously heating to 90 ℃, and carrying out polymerization reaction for 4 hours;
after the reaction, the synthesized white ball was filtered and washed twice with boiling water at 100 ℃ to remove the residual gelatin, glycerin, etc. on the surface of the resin.
Step two, synthesizing heparinized polyacrylic styrene microspheres;
TABLE 2 list of reagents required for the synthesis of heparinized polyacrylic styrene microspheres
The method comprises the following specific operations: firstly, 500mL of acetate buffer solution with the pH value of 3.5-4.0 is prepared, anhydrous zinc chloride is used as a catalyst, the feeding ratio of the polyacrylic styrene microspheres to the heparin sodium is 1:1.5 by mass, the reaction temperature of the solution is 60 ℃, heparinization is carried out on the polyacrylic styrene microspheres, and the heparinization time is about 4 hours, so that the heparinized polyacrylic styrene microspheres are obtained.
Step three, removing the pore-foaming agent and purifying the resin
TABLE 3 list of reagents required for synthetic porogen removal and resin purification
The method comprises the following specific operations:
drying: blowing and drying the synthesized heparinized polyacrylic styrene microspheres for 2-3 hours at the temperature of 60 ℃;
removing the pore-foaming agent: extracting according to the volume ratio of the resin to the petroleum ether of 1:2, replacing the petroleum ether with new petroleum ether, and continuously extracting for 2-4 times to remove the liquid paraffin in the microspheres as much as possible.
③ boiling with water: adding proper amount of water into the adsorbent in a three-neck flask, heating to boil, keeping boiling for 30 min, and repeatedly decocting with water until pH value reaches 5.0-7.0: controlling the residual quantity of liquid wax to be less than 1%;
fourthly, alcohol extraction: replacing the water boiling liquid with alcohol, heating the electric heating jacket until the alcohol boils, keeping the temperature and stirring for about 30 minutes, performing suction filtration, replacing new alcohol, and repeating the steps until the OD value of the adsorbent alcohol washing liquid at the ultraviolet 200-400nm is less than or equal to 0.03;
secondary drying: and (3) after water boiling and alcohol extraction, vacuumizing and drying the heparinized polyacrylic styrene microspheres for 6-8 hours at 60 ℃.
Detailed Description
Example 1
Pore structure characterization of adsorbent materials
TABLE 4 characterization of pore Structure of several batches of LDL resins
| Name of resin | Specific surface area m2/g | Diameter of flat hole nm | Total pore volume ml/g |
| MR20170601 | 489.4 | 4.214 | 1.147 |
| MR20170620 | 496.3 | 4.265 | 1.165 |
| MR20170714 | 501.4 | 4.367 | 1.028 |
Note: a BET pore structure detection method is adopted.
Example 2
Adsorption performance of adsorbent Material
TABLE 5 adsorption Properties of several batches of LDL resins
| Name of resin | Penbarbital sodium | VB12 | β2-MG |
| MR20170601 | 99.98% | 92.45% | 85.47% |
| MR20170620 | 100.02% | 91.59% | 86.54% |
| MR20170714 | 99.55% | 92.15% | 84.98% |
Example 3
Safety performance of adsorption material
Performing small-batch production, processing and canning by using MR20170601 resin with better early-stage adsorption performance to prepare a disposable blood perfusion device, and performing a safety animal whole blood perfusion test;
TABLE 6 adsorption rates of MR20170601 resin on plasma components
| Albumin | Total protein | Blood platelet | White blood cell | Red blood cell |
| 3.8% | 1.7% | 14.8% | 5.9% | 6.1% |
| 3.8% | 1.8% | 14.5% | 6.1% | 6.2% |
| 3.9% | 1.5% | 14.7% | 5.4% | 6.4% |
TABLE 7 electrolyte adsorption Rate of MR20170601 resin pairs
| Potassium salt | Calcium carbonate | Sodium salt | Magnesium alloy | Chlorine | Phosphorus (P) |
| 2.8% | 5.4% | -0.2% | 1.7% | 0.9% | 6.7% |
| 2.9% | 5.5% | 0.1% | 1.8% | 0.5% | 6.5% |
| 2.6% | 5.4% | 0.3% | 1.7% | 0.6% | 6.3% |
Claims (4)
1. A preparation method of a gel type resin material for removing LDL through blood perfusion is characterized by comprising the following steps:
mixing acrylic acid and a divinylbenzene monomer, adding the mixture into an aqueous solution containing a gelatin dispersant and a liquid paraffin pore-foaming agent, adding a glycerol cross-linking agent at the same time, and reacting to obtain pre-crosslinked white polyacrylic acid styrene microspheres;
step two, heparin is adopted to heparinize the pre-crosslinked polyacrylic acid styrene microspheres to obtain heparinized acrylic acid styrene microspheres;
and step three, removing pore-foaming agents and performing alcohol extraction and purification on the polyacrylic styrene microspheres by using petroleum ether and absolute ethyl alcohol respectively to obtain the clean final resin without chloromethyl ether.
2. The method according to claim 1, wherein in the first step, the ratio of acrylic acid to divinylbenzene is 1:2, and the amount of the pore-forming agent is 40-60 wt% of the mixture of styrene and divinylbenzene.
3. The method for preparing a resin material for hemoperfusion-removal of LDL according to claim 1, wherein: in the first step, the pore-foaming agent is liquid paraffin, and benzoyl peroxide is used as an initiator.
4. The method for preparing a resin material for hemoperfusion-removal of LDL according to claim 1, wherein: in the second step, the modifying reagent is heparin.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810111001.1A CN110117379B (en) | 2018-02-05 | 2018-02-05 | Adsorbing material for removing LDL (low density lipoprotein) in blood perfusion and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810111001.1A CN110117379B (en) | 2018-02-05 | 2018-02-05 | Adsorbing material for removing LDL (low density lipoprotein) in blood perfusion and preparation method thereof |
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| Publication Number | Publication Date |
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| CN110117379A CN110117379A (en) | 2019-08-13 |
| CN110117379B true CN110117379B (en) | 2021-11-12 |
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| CN115245606B (en) * | 2021-12-09 | 2024-06-14 | 云南师范大学 | Method for modifying surface of blood perfusion resin microsphere and immobilizing heparin and adsorbent prepared by method |
| CN114426653B (en) * | 2022-01-26 | 2023-12-19 | 河北利江生物科技有限公司 | Be used for adsorbing beta 2 Preparation method and application of resin of-MG (polyethylene glycol) |
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Denomination of invention: A material for removing LDL during blood perfusion and its preparation method Effective date of registration: 20231214 Granted publication date: 20211112 Pledgee: Societe Generale Limited by Share Ltd. Chongqing branch Pledgor: CHONGQING XIERKANG BLOOD PURIFICATION EQUIPMENT RESEARCH DEVELOPMENT CO.,LTD. Registration number: Y2023500000103 |