CN109621912A - A kind of coating method of blood perfusion acticarbon - Google Patents
A kind of coating method of blood perfusion acticarbon Download PDFInfo
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- CN109621912A CN109621912A CN201811569076.0A CN201811569076A CN109621912A CN 109621912 A CN109621912 A CN 109621912A CN 201811569076 A CN201811569076 A CN 201811569076A CN 109621912 A CN109621912 A CN 109621912A
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- active carbon
- chitosan
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- heparin
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- 238000000576 coating method Methods 0.000 title claims abstract description 27
- 230000008081 blood perfusion Effects 0.000 title claims abstract description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 92
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 80
- 229920000669 heparin Polymers 0.000 claims abstract description 37
- 229920001661 Chitosan Polymers 0.000 claims abstract description 36
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 claims abstract description 20
- 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 claims abstract description 17
- 229960001008 heparin sodium Drugs 0.000 claims abstract description 17
- 239000011248 coating agent Substances 0.000 claims abstract description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 49
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
- 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 description 20
- 229960002897 heparin Drugs 0.000 claims description 20
- 229920005989 resin Polymers 0.000 claims description 20
- 239000011347 resin Substances 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 15
- 238000005406 washing Methods 0.000 claims description 12
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 11
- 239000003610 charcoal Substances 0.000 claims description 10
- 238000004132 cross linking Methods 0.000 claims description 10
- 238000010521 absorption reaction Methods 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000003599 detergent Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 230000003213 activating effect Effects 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- -1 Amber acid imide Chemical class 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- 239000003595 mist Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- CHWRSCGUEQEHOH-UHFFFAOYSA-N potassium oxide Chemical compound [O-2].[K+].[K+] CHWRSCGUEQEHOH-UHFFFAOYSA-N 0.000 claims 1
- 229910001950 potassium oxide Inorganic materials 0.000 claims 1
- 239000008280 blood Substances 0.000 abstract description 14
- 210000004369 blood Anatomy 0.000 abstract description 14
- 230000010100 anticoagulation Effects 0.000 abstract description 8
- 239000010408 film Substances 0.000 abstract description 8
- 230000023555 blood coagulation Effects 0.000 abstract description 5
- 239000002245 particle Substances 0.000 abstract description 5
- 230000010412 perfusion Effects 0.000 abstract description 2
- 239000010409 thin film Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 25
- 229960000583 acetic acid Drugs 0.000 description 12
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 10
- 239000003463 adsorbent Substances 0.000 description 9
- 239000008213 purified water Substances 0.000 description 9
- 206010053567 Coagulopathies Diseases 0.000 description 7
- 230000035602 clotting Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 229940109239 creatinine Drugs 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 241000256856 Vespidae Species 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000001951 hemoperfusion Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 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
- 239000004677 Nylon Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004676 glycans Chemical group 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- JKQOBWVOAYFWKG-UHFFFAOYSA-N molybdenum trioxide Chemical compound O=[Mo](=O)=O JKQOBWVOAYFWKG-UHFFFAOYSA-N 0.000 description 1
- 230000008383 multiple organ dysfunction Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920002037 poly(vinyl butyral) polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
- B01J20/20—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising free carbon; comprising carbon obtained by carbonising processes
-
- 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
- A61M1/3621—Extra-corporeal blood circuits
-
- 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
- A61M1/3672—Means preventing coagulation
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/24—Naturally occurring macromolecular compounds, e.g. humic acids or their derivatives
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
- B01J20/28011—Other properties, e.g. density, crush strength
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
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- Organic Chemistry (AREA)
- Anesthesiology (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
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- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- External Artificial Organs (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
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Abstract
The present invention provides a kind of coating method of blood perfusion acticarbon, forms coating film in activated carbon surface with chitosan first, is then crosslinked with epoxychloropropane, increases thin film strength, finally has the heparin sodium of blood coagulation resisting function in film surface grafting.The chitosan film being crosslinked in the present invention can improve the blood compatibility of active carbon, reduce the particles from getting loose of active carbon；Grafting has the heparin sodium of excellent anticoagulation function on film, it is possible to reduce blood and activated carbon surface the phenomenon that blood coagulation occur when contacting, so that improving perfusion device is safety.
Description
Technical field
The present invention relates to a kind of coating methods of blood perfusion acticarbon, belong to blood perfusion field, especially
It is related to a kind of method for improving acticarbon anticoagulant functions.
Background technique
Active carbon is the wide spectrum adsorbent of a kind of porosity, high-specific surface area, and presoma is made through high temperature cabonization, ingredient list
One, chemical stability is good.Active carbon in blood perfusion can adsorb a variety of chemical substances, especially to drug, poisonous substance, with very
High clearance rate, but its blood compatibility is poor, falling off for particle can cause embolism.Therefore, researcher is with having
The high molecular material of preferable blood compatibility coats active carbon, solves acticarbon blood compatibility difference and small carbon granules
The problem of falling off effectively improves the clinical application of active carbon.Active carbon covering material used at present mainly has collodion, gathers
Acrylic hydrogel, poly hydroxy ethyl acrylate, polymethylacrylic acid, polyvinyl butyral, cellulose acetate, nylon,
Gelatin etc..In addition, needing when carrying out blood perfusion in a certain amount of heparin of intravenous injection of patient, progress whole body is anticoagulant, to protect
Card perfusion treatment is gone on smoothly.Although however coating can improve the blood compatibility of active carbon, the anticoagulation energy of adsorbent
Power improvement is very limited, and the interface of adsorbent material and contacting blood is still easy to appear blood coagulation.It may if increasing heparin dosage
Cause uncontrollable bleeding in vivo, or even causes multiple organ dysfunction.Therefore exploitation surface has anticoagulation ability
Adsorbent material is significant to the dosage of reduction heparin, raising Therapeutic safety during hemoperfusion treatment.
Chitosan is product of the chitin after deacetylation, its from a wealth of sources, good biocompatibility can be micro-
Biodegrade is applied in numerous areas such as medicine, food, chemical industry, cosmetics, water process, METAL EXTRACTION and recycling.Shell is poly-
Sugared filming performance is good, by it as the coating agent of hemoperfusion with activated carbon adsorbent material, can improve the blood of absorbent charcoal material
Compatibility reduces particles from getting loose.In addition, can be under given conditions and on heparin sodium molecule containing amino in chitosan molecule chain
Carboxyl reaction, be grafted to heparin sodium molecule in chitosan molecule chain, be expected to improve chitosan material when with contacting blood
Anticoagulation function.
Summary of the invention
The present invention provides a kind of coating method of blood perfusion acticarbon for the defect in the prior art.
Technical problems to be solved are: carrying out coating processing with acticarbon to blood perfusion, solve adsorbent blood compatibility
Difference, particles from getting loose problem, while improving the anticoagulation function of adsorbent.
To reach the above technical effect, a kind of coating method of blood perfusion acticarbon the following steps are included:
Step 1: chitosan is dissolved with acetum, is configured to chitosan solution by coating；Active carbon is then added, stirring makes
Chitosan is sufficiently adsorbed in activated carbon surface；
Step 2: separating and collecting active carbon, remove acetic acid with sodium hydroxide solution detergent active charcoal.
Step 3: crosslinking configures the aqueous slkali of epoxychloropropane, is added step 2 treated active carbon, be stirred to react one
The section time；
Step 4: separating and collecting active carbon, washed with dehydrated alcohol and remove epoxychloropropane.
Step: 5: heparin sodium is dissolved in the PBS solution of pH=5.5 by grafting heparin, when being added one section of activating reagent activation
Between, step 2 gained active carbon is then added, at room temperature stirring sufficiently reaction.
Step 6: separating and collecting active carbon, with purifying water washing, remove the heparin of physical absorption, finally drying is obtained into
Product.
Further, the active carbon for coating can have for column, sheet or spherical without sharp corner angle
Some strength micro mist is not easily to fall off.Preferred active carbon is spherical resin carbon.
Further, the mass concentration of chitosan is 3% ~ 5% in the step 1, and the mass concentration of acetic acid is 2% ~ 5%.
Further, the volume ratio of active carbon and chitosan solution is 1:1 ~ 2 in the step 1, and active carbon stirring is added
Adsorption time is 0.5 ~ 1h.
Further, the concentration of washing sodium hydroxide solution is 0.1mol/L ~ 1mol/L in the step 2.
Further, the concentration of epoxychloropropane is 0.5mol/L ~ 1.0mol/L in the step 3, and the lye is hydrogen
Sodium oxide molybdena or Strong oxdiative potassium solution, solution PH=10.
Further, the volume ratio of active carbon and epoxychloropropane solution is 1:1 ~ 2 in the step 3, and reaction temperature is
40 DEG C ~ 60 DEG C, the reaction time is 2 ~ 4h.
Further, the concentration of heparin sodium is 0.5 ~ 1g/L, PBS solution PH=5.5 in the step 5.
Further, activating reagent is n-hydroxysuccinimide (NHS) and (3- that mass ratio is 1:3 in the step 5
Dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride (EDC-HCl), wherein the concentration of NHS is 0.5g/L；Activation time is
0.5~1h。
Further, the volume ratio of active carbon and heparin sodium aqua is 1:1 ~ 2 in the step 3, and being stirred to react the time is 6
~12h。
Further, the step 2, the method for isolating active charcoal can be centrifugation or filtering in 4,6.
Based on the above, the present invention provides a kind of coating method of blood perfusion acticarbon, uses shell first
Glycan forms coating film in activated carbon surface, is then crosslinked with epoxychloropropane, increases thin film strength, finally in film surface
It is grafted the heparin sodium with blood coagulation resisting function.The chitosan film being crosslinked in the present invention can improve the blood compatibility of active carbon
Property, reduce the particles from getting loose of active carbon；Grafting has the heparin sodium of excellent anticoagulation function on film, it is possible to reduce blood and work
Property carbon surface contact when there is the phenomenon that blood coagulation, to improve the anticoagulation function of adsorbent.
Specific embodiment
The following specific embodiments are described below, is further explained to the present invention:
Embodiment 1:
A kind of coating method of blood perfusion acticarbon is using spherical resin carbon as raw material, comprising the following steps:
Step 1: coating, 4.5g chitosan are dispersed in 150ml purified water, and glacial acetic acid then is added according to mass concentration 3%, stirs
Mixing is completely dissolved chitosan；Subsequent 100ml resin carbon, stirring 2h adsorb chitosan sufficiently in resin carbon surface；
Step 2: active carbon is collected by filtration, removes acetic acid with the sodium hydroxide solution detergent active charcoal of 0.5mol/L.
Step 3: the epoxychloropropane of 0.15mol is dissolved in the sodium hydroxide solution (PH=10) of 150ml, then by crosslinking
Step 1 treated active carbon is added, 40 DEG C are stirred to react 4h；
Step 4: active carbon is collected by filtration, is washed with dehydrated alcohol and removes epoxychloropropane, then with purified water active carbon to washing
Liquid is washed to be in neutrality.
Step: 5: 75mg heparin sodium is dissolved in PBS (pH5.5) solution of 150 mL, 75mg is then added by grafting heparin
N-hydroxysuccinimide (NHS) and 225mg(3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride (EDC-HCl), it is living
Change 1h, step 2 gained active carbon is then added, stirs 6h at room temperature.
Step 6: active carbon is collected by filtration, with purifying water washing, removes the heparin of physical absorption, finally drying is obtained into
Product.
Embodiment 2:
A kind of coating method of blood perfusion acticarbon is using spherical resin carbon as raw material, comprising the following steps:
Step 1: coating, 6.0g chitosan are dispersed in 150ml purified water, and glacial acetic acid then is added according to mass concentration 3%, stirs
Mixing is completely dissolved chitosan；Subsequent 100ml resin carbon, stirring 2h adsorb chitosan sufficiently in resin carbon surface；
Step 2: active carbon is collected by filtration, removes acetic acid with the sodium hydroxide solution detergent active charcoal of 0.5mol/L.
Step 3: the epoxychloropropane of 0.15mol is dissolved in the sodium hydroxide solution (PH=10) of 150ml, then by crosslinking
Step 1 treated active carbon is added, 50 DEG C are stirred to react 4h；
Step 4: active carbon is collected by filtration, is washed with dehydrated alcohol and removes epoxychloropropane, then with purified water active carbon to washing
Liquid is washed to be in neutrality.
Step: 5: 150mg heparin sodium is dissolved in PBS (pH5.5) solution of 150 mL, is then added by grafting heparin
75mg n-hydroxysuccinimide (NHS) and 225mg(3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride (EDC-
HCl), 1h is activated, step 2 gained active carbon is then added, stirs 6h at room temperature.
Step 6: active carbon is collected by filtration, with purifying water washing, removes the heparin of physical absorption, finally drying is obtained into
Product.
Embodiment 3:
A kind of coating method of blood perfusion acticarbon is using spherical resin carbon as raw material, comprising the following steps:
Step 1: coating, 7.5g chitosan are dispersed in 150ml purified water, and glacial acetic acid then is added according to mass concentration 3%, stirs
Mixing is completely dissolved chitosan；Subsequent 100ml resin carbon, stirring 2h adsorb chitosan sufficiently in resin carbon surface；
Step 2: active carbon is collected by filtration, removes acetic acid with the sodium hydroxide solution detergent active charcoal of 0.5mol/L.
Step 3: the epoxychloropropane of 0.15mol is dissolved in the sodium hydroxide solution (PH=10) of 150ml, then by crosslinking
Step 1 treated active carbon is added, 60 DEG C are stirred to react 4h；
Step 4: active carbon is collected by filtration, is washed with dehydrated alcohol and removes epoxychloropropane, then with purified water active carbon to washing
Liquid is washed to be in neutrality.
Step: 5: 150mg heparin sodium is dissolved in PBS (pH5.5) solution of 150 mL, is then added by grafting heparin
75mg n-hydroxysuccinimide (NHS) and 225mg(3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride (EDC-
HCl), 1h is activated, step 2 gained active carbon is then added, stirs 6h at room temperature.
Step 6: active carbon is collected by filtration, with purifying water washing, removes the heparin of physical absorption, finally drying is obtained into
Product.
Embodiment 4:
A kind of coating method of blood perfusion acticarbon is using spherical resin carbon as raw material, comprising the following steps:
Step 1: coating, 7.5g chitosan are dispersed in 150ml purified water, and glacial acetic acid then is added according to mass concentration 3%, stirs
Mixing is completely dissolved chitosan；Subsequent 100ml resin carbon, stirring 2h adsorb chitosan sufficiently in resin carbon surface；
Step 2: active carbon is collected by filtration, removes acetic acid with the sodium hydroxide solution detergent active charcoal of 0.5mol/L.
Step 3: the epoxychloropropane of 0.075mol is dissolved in the sodium hydroxide solution (PH=10) of 150ml by crosslinking, with
Step 1 treated active carbon is added afterwards, 60 DEG C are stirred to react 4h；
Step 4: active carbon is collected by filtration, is washed with dehydrated alcohol and removes epoxychloropropane, then with purified water active carbon to washing
Liquid is washed to be in neutrality.
Step: 5: 150mg heparin sodium is dissolved in PBS (pH5.5) solution of 150 mL, is then added by grafting heparin
75mg n-hydroxysuccinimide (NHS) and 225mg(3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride (EDC-
HCl), 1h is activated, step 2 gained active carbon is then added, stirs 12h at room temperature.
Step 6: active carbon is collected by filtration, with purifying water washing, removes the heparin of physical absorption, finally drying is obtained into
Product.
Embodiment 5:
The absorption property of sample is tested: according to the absorption property of standard YY 0464-2009 " disposable blood perfusion device "
Absorption property of the test method test sample to yellow Jackets, creatinine and VB12.
Embodiment 6:
Full clotting assay: sample to be tested 1ml is added in teat glass, with physiological saline rinse 3 times, is then added along tube wall
The new fresh rabbit blood of 2ml.Test tube is tilted every 0.5min after 3min, until the blood in value test tube does not flow, the time at this time is denoted as
Clotting time.
Comparative example:
(1) comparative example 1: not do the resin carbon of any processing as a comparison case 1；
(2) comparative example 2: carrying out resin carbon chitosan coated, is not grafted heparin as a comparison case 2.It is specific the preparation method comprises the following steps:
1. 7.5g chitosan is dispersed in 150ml purified water, glacial acetic acid then is added according to mass concentration 3%, stirring makes chitosan
It is completely dissolved；Subsequent 100ml resin carbon, stirring 2h adsorb chitosan sufficiently in resin carbon surface；
2. active carbon is collected by filtration, unreacted acetic acid is removed with the sodium hydroxide solution detergent active charcoal of 0.5mol/L；
3. being crosslinked, the epoxychloropropane of 0.075mol is dissolved in the sodium hydroxide solution (PH=10) of 150ml, step is then added
Rapid 1 treated active carbon, 60 DEG C are stirred to react 4h；
Test result is as follows shown in table for the end properties of each embodiment preparation:
Upper table statistics indicate that: 1. each embodiment compared with comparative example 1, processing meeting of the invention so that resin carbon to creatinine, penta bar
Adsorbance than appropriate sodium, VB12 declines, but the clotting time can be obviously prolonged；2. embodiment 1,2,3 is chitosan coated
The concentration of solution successively increases, and membrane wrapping thickness increases, and successively declines to the adsorbance of creatinine, yellow Jackets, VB12；But heparin
Grafting amount it is successively also primary increase, therefore the clotting time also successively extends；3. embodiment 4 is compared with Example 3, used in crosslinking
Epoxychloropropane concentration it is low, crosslinking degree is relatively weak, and the amino for consuming chitosan is few, allow heparin be grafted when have
More amino participate in reaction, and heparin grafting amount is bigger, and reaction is obviously prolonged in clotting time embodiment 4；4. embodiment 4 with it is right
Ratio 2 is compared, and carries out coating with the chitosan solution of same concentration, crosslinker concentration and crosslinking condition are also identical, but embodiment
Four have carried out heparin grafting.Therefore the clotting time of embodiment 4 is obviously long with comparative example 2, but creatinine, yellow Jackets,
The adsorbance of VB12 is not much different with comparative example 2.
In conclusion resin carbon is handled using coating method of the invention, although the suction of creatinine, yellow Jackets, VB12
Attached amount is declined, but can be obviously prolonged the clotting time, improves the anticoagulation function of adsorbent.Change can be passed through simultaneously
Parameter in the process, adjusts the grafting amount of the thickness of coating, the degree of crosslinking and heparin sodium, to control the adsorptivity of finished product
Needs can be met with security performance.
Concrete mode of the invention is described in detail above, but it is merely an example, the present invention is not limited to
Embodiments above.To those skilled in the art, any couple of present invention carry out equivalent modifications and substitution also all exist
Among scope of the invention.Therefore, in the equal transformation and modification made without departing from the spirit and scope of the invention, should all contain
Lid is within the scope of the present invention.
Claims (11)
1. a kind of coating method of blood perfusion acticarbon, it is characterised in that the following steps are included:
Step 1: chitosan is dissolved with acetum, is configured to chitosan solution by coating；Active carbon is then added, stirring makes
Chitosan is sufficiently adsorbed in activated carbon surface；
Step 2: separating and collecting active carbon, with sodium hydroxide solution detergent active charcoal, remove acetic acid；
Step 3: crosslinking configures the aqueous slkali of epoxychloropropane, step 2 is added treated active carbon, when being stirred to react one section
Between；
Step 4: separating and collecting active carbon, washed with dehydrated alcohol and remove epoxychloropropane；
Step: 5: heparin sodium is dissolved in the PBS solution of pH=5.5 by grafting heparin, and activating reagent activation a period of time is added, with
Step 2 gained active carbon is added afterwards, at room temperature stirring sufficiently reaction；
Step 6: separating and collecting active carbon, with purifying water washing, remove the heparin of physical absorption, finally drying obtains finished product.
2. according to described in claim 1, it is characterised in that the active carbon for coating can be column, sheet or ball
Shape has some strength micro mist not easily to fall off without sharp corner angle, including but not limited to spherical resin carbon.
3. according to described in claim 1, it is characterised in that the mass concentration of chitosan is 3% ~ 5% in the step 1, the matter of acetic acid
Measuring concentration is 2% ~ 5%.
4. according to described in claim 1, it is characterised in that in the step 1 volume ratio of active carbon and chitosan solution be 1:1 ~
2, the addition active carbon stirring and adsorbing time is 0.5 ~ 1h.
5. according to described in claim 1, it is characterised in that the concentration of washing sodium hydroxide solution is in the step 2
0.1mol/L~1mol/L。
6. according to described in claim 1, it is characterised in that in the step 3 concentration of epoxychloropropane be 0.5mol/L ~
1.0mol/L, the lye are sodium hydroxide or potassium oxide solution, solution PH=10.
7. according to described in claim 1, it is characterised in that the volume ratio of active carbon and epoxychloropropane solution is in the step 3
1:1 ~ 2, reaction temperature are 40 DEG C ~ 60 DEG C, and the reaction time is 2 ~ 4h.
8. according to described in claim 1, it is characterised in that the concentration of heparin sodium is 0.5 ~ 1g/L, PBS solution PH in the step 5
=5.5。
9. according to described in claim 1, it is characterised in that activating reagent is the N- hydroxyl amber that mass ratio is 1:3 in the step 5
Amber acid imide (NHS) and (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride (EDC-HCl), wherein the concentration of NHS be
0.5g/L；Activation time is 0.5 ~ 1h.
10. according to described in claim 1, it is characterised in that the volume ratio of active carbon and heparin sodium aqua is 1:1 in the step 3
~ 2, being stirred to react the time is 6 ~ 12h.
11. according to described in claim 1, it is characterised in that the step 2, the method for isolating active charcoal can be centrifugation in 4,6
Or filtering.
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| CN112439397A (en) * | 2019-08-28 | 2021-03-05 | 云南师范大学 | Blood perfusion adsorbent coated and immobilized with heparin and preparation method thereof |
| CN112473636A (en) * | 2019-09-11 | 2021-03-12 | 云南师范大学 | Blood perfusion adsorbent coated and covalently fixed with heparin and preparation method thereof |
| CN113385151A (en) * | 2021-05-27 | 2021-09-14 | 北京中科盛康科技有限公司 | Intelligent resin coating process system for blood perfusion device |
| CN113600148A (en) * | 2021-08-10 | 2021-11-05 | 四川大学华西医院 | Heparin-modified chitosan/cellulose microsphere-based hemoperfusion adsorbent, preparation method and application thereof |
| CN114288997A (en) * | 2021-12-16 | 2022-04-08 | 健帆生物科技集团股份有限公司 | Adsorption resin with self-anticoagulation property and preparation method and application thereof |
| CN118122277A (en) * | 2024-03-06 | 2024-06-04 | 重庆希尔康血液净化器材研发有限公司 | Perfusion resin grafted with sodium citrate and preparation process thereof |
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| CN112439397A (en) * | 2019-08-28 | 2021-03-05 | 云南师范大学 | Blood perfusion adsorbent coated and immobilized with heparin and preparation method thereof |
| CN112473636A (en) * | 2019-09-11 | 2021-03-12 | 云南师范大学 | Blood perfusion adsorbent coated and covalently fixed with heparin and preparation method thereof |
| CN110841602A (en) * | 2019-09-30 | 2020-02-28 | 佛山市博新生物科技有限公司 | Blood purification material based on mussel bionic chemistry and preparation method thereof |
| CN110841602B (en) * | 2019-09-30 | 2022-08-05 | 佛山市博新生物科技有限公司 | Blood purification material based on mussel bionic chemistry and preparation method thereof |
| CN113385151A (en) * | 2021-05-27 | 2021-09-14 | 北京中科盛康科技有限公司 | Intelligent resin coating process system for blood perfusion device |
| CN113600148A (en) * | 2021-08-10 | 2021-11-05 | 四川大学华西医院 | Heparin-modified chitosan/cellulose microsphere-based hemoperfusion adsorbent, preparation method and application thereof |
| CN113600148B (en) * | 2021-08-10 | 2022-08-12 | 四川大学华西医院 | Heparin-modified chitosan/cellulose microsphere-based hemoperfusion adsorbent, preparation method and application thereof |
| CN114288997A (en) * | 2021-12-16 | 2022-04-08 | 健帆生物科技集团股份有限公司 | Adsorption resin with self-anticoagulation property and preparation method and application thereof |
| CN118122277A (en) * | 2024-03-06 | 2024-06-04 | 重庆希尔康血液净化器材研发有限公司 | Perfusion resin grafted with sodium citrate and preparation process thereof |
| CN118122277B (en) * | 2024-03-06 | 2025-01-10 | 重庆希尔康血液净化器材研发有限公司 | Perfusion resin grafted with sodium citrate and preparation process thereof |
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