CN105126787A - Method for improving anticoagulant activity of adsorbent - Google Patents
Method for improving anticoagulant activity of adsorbent Download PDFInfo
- Publication number
- CN105126787A CN105126787A CN201510482480.4A CN201510482480A CN105126787A CN 105126787 A CN105126787 A CN 105126787A CN 201510482480 A CN201510482480 A CN 201510482480A CN 105126787 A CN105126787 A CN 105126787A
- Authority
- CN
- China
- Prior art keywords
- adsorbent
- anticoagulant
- diamines
- heparin
- coagulants
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000003463 adsorbent Substances 0.000 title claims abstract description 84
- 238000000034 method Methods 0.000 title claims abstract description 56
- 230000014508 negative regulation of coagulation Effects 0.000 title abstract 2
- 239000003146 anticoagulant agent Substances 0.000 claims abstract description 29
- 229940127219 anticoagulant drug Drugs 0.000 claims abstract description 29
- 229920000669 heparin Polymers 0.000 claims abstract description 20
- 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 16
- 229960002897 heparin Drugs 0.000 claims abstract description 16
- 230000010100 anticoagulation Effects 0.000 claims abstract description 15
- 230000002429 anti-coagulating effect Effects 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 16
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 claims description 14
- 150000004985 diamines Chemical class 0.000 claims description 13
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 7
- 238000004140 cleaning Methods 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 6
- 239000001509 sodium citrate Substances 0.000 claims description 6
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 229920000936 Agarose Polymers 0.000 claims description 4
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 4
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 4
- 239000004005 microsphere Substances 0.000 claims description 4
- 230000003204 osmotic effect Effects 0.000 claims description 4
- 229920000193 polymethacrylate Polymers 0.000 claims description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 239000011325 microbead Substances 0.000 claims description 3
- 239000011859 microparticle Substances 0.000 claims description 3
- 229920000573 polyethylene Polymers 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims 1
- 210000004369 blood Anatomy 0.000 abstract description 15
- 239000008280 blood Substances 0.000 abstract description 15
- 230000001954 sterilising effect Effects 0.000 abstract description 12
- 230000008569 process Effects 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 7
- 238000004659 sterilization and disinfection Methods 0.000 abstract description 7
- 229920000642 polymer Polymers 0.000 abstract description 5
- 230000023555 blood coagulation Effects 0.000 abstract description 4
- 238000003860 storage Methods 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 3
- 238000004132 cross linking Methods 0.000 abstract description 2
- 230000009469 supplementation Effects 0.000 abstract 1
- 230000006872 improvement Effects 0.000 description 18
- 238000007710 freezing Methods 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000032683 aging Effects 0.000 description 8
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000002158 endotoxin Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229960001484 edetic acid Drugs 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000011938 amidation process Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005191 phase separation Methods 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 2
- 230000009514 concussion Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 235000002710 Ilex cornuta Nutrition 0.000 description 1
- 241001310146 Ilex cornuta Species 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
- 235000010326 Osmanthus heterophyllus Nutrition 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 231100000284 endotoxic Toxicity 0.000 description 1
- 230000002346 endotoxic effect Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000011540 sensing material Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
Landscapes
- External Artificial Organs (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Belonging to the field of medical instruments, the invention discloses a method for improving the anticoagulant activity of an adsorbent. According to the method, an anticoagulant is subjected to crosslinking so as to form an interpenetrating polymer network with an initial adsorbent, the anticoagulant stability of the adsorbent is greatly improved, and the finally prepared adsorbent can tolerate sterilization treatment, and the storage stability is also very good. According to the adsorbent obtained by treatment of the method, no chemical bond effect exists between the crosslinked anticoagulant and the adsorbent, and the moving range is limited only by the interpenetrating network cross structure. And by means of the interpenetrating network structure, the anticoagulant can be distributed throughout the internal and external structure of the adsorbent to reach an ideal anticoagulation effect. Therefore, the dosage of heparin can be effectively reduced in the treatment process, or even supplementation of heparin is unnecessary, the blood compatibility of the adsorbent is improved, then the safety of the adsorbent is enhanced, and the risks of blood coagulation and the like in clinical treatment can be reduced.
Description
Technical field
The present invention relates to a kind of method improving adsorbent anticoagulant property, particularly a kind of method improving adsorbent anticoagulant property based on interpenetrating networks.
Background technology
Blood index therapy mainly utilizes adsorbent to purge away the poison in one's blood and morbid substance, thus reaches and purify the blood, and alleviates, the object of disease therapy.Blood index therapy has obvious curative effect clinically, is current indispensable a kind of methods for the treatment of.
Often need to carry out heparinize process to treatment pipeline and adsorbent in Clinical practice, to improve the anticoagulation function of adsorbent, and also need over the course for the treatment of to add heparin.This needs medical personnel need regulate the consumption of anti-coagulants according to the situation of patient, and operation easier is also increased.
Conventional anti-coagulants has heparin, sodium citrate and ethylenediamine tetra-acetic acid (EDTA) etc.Its anti-freezing principle of different anti-coagulants is different.Ethylenediamine tetra-acetic acid (EDTA) is identical with the anti-freezing principle of citrate: be become chelate with calcium binding in blood, calcium is lost activity, and interrupts coagulation process, thus reaches the object of anti-freezing.Heparin is then by strengthening antithrombin Ⅲ, deactivation serine protease, stops the formation of fibrin ferment to reach the object of anti-freezing.
In the open scheme of CN102127204A, by surface of elastomer grafting heparin, prepare the compound polyether-polyurethane material with anticoagulation function.Also have and utilize temperature sensing material to prepare the gel release heparin of spansule to reach the object improving anti-freezing performance, but its sterilizing, transport storage process also may cause anti-coagulants discharge in advance and fall effect, as medical material, need through strict sterilization treatment, prior art generally adopts high temperature, high pressure or the sterilizing of the Disinfection Methods such as ultraviolet, irradiation, but these measures can have destruction to heparin.The anticoagulant property of product is caused to decline.
Therefore, develop a kind of method being applicable to improve various adsorbent anticoagulation function and there is very actual meaning.
Summary of the invention
The object of the present invention is to provide a kind of method improving Blood index therapy adsorbent anticoagulant property.
The technical solution used in the present invention is:
Improve a method for adsorbent anticoagulant property, comprise the steps:
1) by adsorbent, anti-coagulants, solvent mixing, mixed liquor is obtained;
2) regulate the pH of mixed liquor, add acid amides catalysts, drip two amine aqueous solutions, react completely;
3) cleaning reaction product, obtains the adsorbent of highly blood coagulation resistant.
As the further improvement of said method, solvent is water or the water being added with osmotic pressure regulator.
As the further improvement of said method, acid amides catalysts is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride.
As the further improvement of said method, in mixed liquor, the concentration of anticoagulant is 0.1 ~ 100mg/mL.
As the further improvement of said method, in two amine aqueous solutions, the mass percentage concentration 0.005 ~ 0.1% of diamines.
As the further improvement of said method, the mol ratio of anticoagulant and diamines is 1:(0.01 ~ 0.2).
As the further improvement of said method, anticoagulant is selected from heparin, disodium ethylene diamine tetraacetate or sodium citrate.
As the further improvement of said method, two amine aqueous solutions are the aqueous solution of diamines.
As the further improvement of said method, diamines is hexamethylene diamine.
As the further improvement of said method, adsorbent is selected from polystyrene divinylbenzene adsorbent, polymethacrylates adsorbent, agarose microbeads adsorbent, polyvinyl alcohol microparticles, cellulose microsphere, polythene strip tabular adsorbent.
The invention has the beneficial effects as follows:
Method of the present invention, by being cross-linked by anti-coagulants, forming interpenetrating net polymer with initial adsorption agent, significantly improve the stability of anticoagulant, the adsorbent finally prepared can tolerate sterilization treatment, and the stability of storage is also fine.
The adsorbent that the inventive method process obtains, the crosslinked effect that there is no chemical bond between anti-coagulants and adsorbent, just limits its moving range by interpenetrating networks chi structure.And by inierpeneirating network structure, anti-coagulants can be made to run through the external and internal compositions being distributed in adsorbent, ideal anticoagulant effect can be reached.This effectively can reduce heparin consumption over the course for the treatment of, not even with adding heparin, improves the blood compatibility of adsorbent, and then improves the security of adsorbent, is reduced in clinical treatment and occurs blood coagulation equivalent risk.
The adsorbent that the inventive method process obtains, the size of the micro phase separation structure formed between adsorbent and crosslinked anti-coagulants has between tens to one hundred nanometer, can be conducive to adsorbent and intercept the lps molecules such as the endotoxin (1 ~ 50nm) in blood.These micro phase separation structure energy inhibition thrombosis, have good anticoagulant property.
The inventive method can carry out the crosslinking Treatment of interpenetrating networks to the adsorbent of various forms blood purification (as crosslinked microsphere, film, plate), utilize the structure forming interpenetrating net polymer, can modify various adsorbent, improve its blood compatibility, and then improve the security of blood purification material.
Accompanying drawing explanation
Fig. 1 is the result of accelerated aging tests.
Detailed description of the invention
Improve a method for adsorbent anticoagulant property, comprise the steps:
1) by adsorbent, anti-coagulants, solvent mixing, mixed liquor is obtained;
2) regulate the pH of mixed liquor, add acid amides catalysts, drip two amine aqueous solutions, react completely;
3) cleaning reaction product, obtains the adsorbent of highly blood coagulation resistant.
As the further improvement of said method, solvent is water or the water being added with osmotic pressure regulator.Osmotic pressure regulator is preferably NaCl.
1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride can catalysis amidation process in a mild condition, and therefore, as the further improvement of said method, acid amides catalysts is EDC.
The pH of acid amides reaction can be well known to those skilled in the art, and especially, pH is preferably 4 ~ 6.
In order to avoid, amidation process is too fast causes reaction uneven, and as the further improvement of said method, in mixed liquor, the concentration of anticoagulant is 0.1 ~ 100mg/mL.Its concentration can regulate accordingly according to real reaction situation.
In order to avoid, amidation process is too fast causes reaction uneven, as the further improvement of said method, in two amine aqueous solutions, and the mass percentage concentration 0.005 ~ 0.1% of diamines.
For ensure diamines can total overall reaction completely and have part anti-coagulants to dissociate simultaneously, anti-coagulants should excessive interpolation.As the further improvement of said method, the mol ratio of anticoagulant and diamines is 1:(0.01 ~ 0.2).
As the further improvement of said method, anticoagulant is selected from heparin, disodium ethylene diamine tetraacetate or sodium citrate.
As the further improvement of said method, two amine aqueous solutions are the aqueous solution of diamines.
As the further improvement of said method, diamines is hexamethylene diamine.
Adsorbent is known adsorbent in the industry, and its shape, without particular/special requirement, can be tabular, spherical and film etc.As the further improvement of said method, adsorbent is selected from polystyrene divinylbenzene adsorbent, polymethacrylates adsorbent, agarose, polyvinyl alcohol microparticles, cellulose microsphere, polythene strip tabular adsorbent.
Below in conjunction with embodiment, further illustrate technical scheme of the present invention.
Embodiment 1
Get a certain amount of polystyrene divinylbenzene adsorbent, add the physiological saline 50mL of 100mg/500mL heparin, then pH is regulated to be 4.8, add 0.01g1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC), be added dropwise to the aqueous solution containing 0.01% hexamethylene diamine, in 25 DEG C, shake reaction 4 hours.Rear alcohol, injection water cleaning are reacted.
Embodiment 2
Get a certain amount of polystyrene divinylbenzene adsorbent, add the normal saline solution 50mL of 3.8% sodium citrate, then pH is regulated to be 4, add 0.01g1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC), be added dropwise to the aqueous solution containing 0.05% hexamethylene diamine, in 25 DEG C, shake reaction 4 hours.Rear alcohol, injection water cleaning are reacted.
Embodiment 3
Get a certain amount of polymethacrylates adsorbent, add the normal saline solution 50mL of 15g/L disodium ethylene diamine tetraacetate, then pH is regulated to be 4.8, add 0.008g1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC), be added dropwise to the aqueous solution containing 0.05% hexamethylene diamine, in 25 DEG C, shake reaction 4 hours.Rear alcohol, injection water cleaning are reacted.
Embodiment 4
Get a certain amount of agarose microbeads adsorbent, add the normal saline solution 50mL of 3.8% sodium citrate, then pH is regulated to be 6, add 0.015g1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC), be added dropwise to the aqueous solution containing 0.06% hexamethylene diamine, in 25 DEG C, shake reaction 4 hours.Rear alcohol, injection water cleaning are reacted.
Anticoagulant effect compares
Anticoagulation function is evaluated with recalcification time.Detection method: extract health adult venous blood 3.6mL, puts into 3.2% Chinese holly edge acid sodium anticoagulant tube, sends into centrifuge with the centrifugal l0min separated plasma of 3000r/m; Respectively a certain amount of adsorbent is put into clean teat glass, add 0.4mL blood plasma, 37 DEG C of water-baths 1 minute; Add the 0.4mL0.025mol/LCaCl of 37 DEG C of preheatings again
2, 37 DEG C of water-baths; There is the time of the fine floccule of Article 1 in record teat glass, be recalcification time.Experimental result is as shown in table 1.
Table 1 recalcification time experimental result
Recalcification time extends, and shows that material anticoagulant effect is good.The recalcification time being cross-linked anti-freezing adsorbent by the visible IPN of table 1 is longer, and namely its anticoagulant effect is obviously good than common adsorbent, and very nearly the same with the anticoagulant effect of heparinize adsorbent.
After sterilizing, anticoagulant effect compares
Get polystyrene divinylbenzene adsorbent and carry out moist heat sterilization process (121 DEG C, 1h), then the absorbent measuring recalcification time contrasted before and after sterilizing is with par anticoagulation function.
Table 2 recalcification time experimental result
Contrast table 1 and table 2 can find that the adsorbent of direct heparinize is after sterilization treatment, and recalcification time shortens, and namely anticoagulation function obviously declines to some extent.And IPN is cross-linked anti-freezing adsorbent after sterilizing, recalcification time does not change substantially, namely anticoagulation function does not significantly decrease, and illustrates that this method can improve the anticoagulation function of adsorbent effectively, and can stand sterilization treatment and substantially not affect its anticoagulation function.
Accelerated ageing affects anticoagulation function
According to American Society for Testing and Materials standard A STMF1980-07 " aseptic medical equipment packaging accelerated aging test standard guide ", this perfusion device degradation, it is exactly theoretical according to accelerated ageing and Arrhenius formula, recommend by it, store 53 days at 60 DEG C of accelerated ageing temperature, store 2 years at being just equal to actual environment temperature 22 DEG C.Get the adsorbent after sterilizing and carry out accelerated aging tests, evaluate the change of its anticoagulation ability within 2 years with recalcification time, its result as shown in Figure 1.
As seen from Figure 1, through the accelerated ageing of 2 years, the adsorbent (polystyrene divinylbenzene adsorbent through anti-freezing process that embodiment 1 finally prepare) crosslinked through IPN still can maintain good anticoagulation function.And its anticoagulation function after the accelerated ageing of half a year directly adding heparin is substantially the same with virgin sorbent, this does not reach the effect of production application requirement anti-freezing performance.The adsorbent of visible formation interpenetrating net polymer keeps anticoagulant effect to have clear superiority in storage etc.
Static Adsorption endotoxin is tested
Get test tube, add the adsorbent 0.25mL of adsorbent and formation interpenetrating net polymer respectively, then add containing endotoxic blood plasma 1.5mL, concussion absorption 2 hours (temperature 37 DEG C, concussion speed 100 ± 10rpm), then detectable concentration, and calculate adsorbent to its clearance rate.
The adsorbance of table 3 adsorbent induced by endotoxin and clearance rate
From the data of table 3, after adsorbent forms IPN cross-linked structure, the adsorption removal ability of adsorbent induced by endotoxin increases.This may be that the size of micro phase separation structure owing to being formed between adsorbent and crosslinked anti-coagulants reaches tens to one hundred nanometer, is conducive to intercepting the macromolecular toxins such as the endotoxin in blood, and improves the blood compatibility of adsorbent.
In table 1 ~ 3, adsorbent is the polystyrene divinylbenzene adsorbent without anti-freezing process in embodiment 1, and heparinize adsorbent is the polystyrene divinylbenzene adsorbent being added with 100mg/500mL heparin; It is the polystyrene divinylbenzene adsorbent through anti-freezing process that embodiment 1 finally prepares that IPN is cross-linked anti-freezing adsorbent.
Claims (10)
1. improve a method for adsorbent anticoagulant property, comprise the steps:
By adsorbent, anti-coagulants, solvent mixing, obtain mixed liquor;
Regulate the pH of mixed liquor, add acid amides catalysts, drip two amine aqueous solutions, react completely;
Cleaning reaction product, obtains the adsorbent that anticoagulation function is good.
2. method according to claim 1, is characterized in that: solvent is water or the water being added with osmotic pressure regulator.
3. method according to claim 1, is characterized in that: acid amides catalysts is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride.
4. method according to claim 1, is characterized in that: in mixed liquor, and the concentration of anti-coagulants is 0.1 ~ 100mg/mL.
5. the method according to claim 1 or 4, is characterized in that: in two amine aqueous solutions, the mass percentage concentration 0.005 ~ 0.1% of diamines.
6. the method according to claim 1 or 4, is characterized in that: the mol ratio of anticoagulant and diamines is 1:(0.01 ~ 0.2).
7. the method according to Claims 1 to 4 any one, is characterized in that: anticoagulant is selected from heparin, disodium ethylene diamine tetraacetate or sodium citrate.
8. the method according to Claims 1 to 4 any one, is characterized in that: two amine aqueous solutions are the aqueous solution of diamines.
9. the method according to Claims 1 to 4 any one, is characterized in that: diamines is hexamethylene diamine.
10. the method according to Claims 1 to 4 any one, is characterized in that: adsorbent is selected from polystyrene divinylbenzene adsorbent, polymethacrylates adsorbent, agarose microbeads adsorbent, polyvinyl alcohol microparticles, cellulose microsphere, polythene strip tabular adsorbent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510482480.4A CN105126787B (en) | 2015-08-03 | 2015-08-03 | A kind of method for improving adsorbent anticoagulant property |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510482480.4A CN105126787B (en) | 2015-08-03 | 2015-08-03 | A kind of method for improving adsorbent anticoagulant property |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105126787A true CN105126787A (en) | 2015-12-09 |
| CN105126787B CN105126787B (en) | 2017-06-06 |
Family
ID=54712560
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510482480.4A Active CN105126787B (en) | 2015-08-03 | 2015-08-03 | A kind of method for improving adsorbent anticoagulant property |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105126787B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109692371A (en) * | 2019-01-28 | 2019-04-30 | 四川大学 | It is a kind of from anticoagulant double-layer active carbon blood perfusion device and blood perfusion method |
| JP2020092879A (en) * | 2018-12-13 | 2020-06-18 | 東レ株式会社 | Blood purification column |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5413697A (en) * | 1977-06-30 | 1979-02-01 | Nissho Kk | Blood purifying adsorber |
| CN1528511A (en) * | 2003-09-27 | 2004-09-15 | 南开大学 | Endotoxin adsorbent and preparation method thereof |
| CN1799649A (en) * | 2005-12-09 | 2006-07-12 | 清华大学 | Blood compatible biological material and preparation method thereof |
| CN101623622A (en) * | 2009-07-28 | 2010-01-13 | 中国科学院上海硅酸盐研究所 | Absorbent material and preparation thereof |
| CN103230781A (en) * | 2013-05-03 | 2013-08-07 | 重庆大学 | Heparin-phenylalanine adsorption material for blood purification method for removing endotoxin |
-
2015
- 2015-08-03 CN CN201510482480.4A patent/CN105126787B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5413697A (en) * | 1977-06-30 | 1979-02-01 | Nissho Kk | Blood purifying adsorber |
| CN1528511A (en) * | 2003-09-27 | 2004-09-15 | 南开大学 | Endotoxin adsorbent and preparation method thereof |
| CN1799649A (en) * | 2005-12-09 | 2006-07-12 | 清华大学 | Blood compatible biological material and preparation method thereof |
| CN101623622A (en) * | 2009-07-28 | 2010-01-13 | 中国科学院上海硅酸盐研究所 | Absorbent material and preparation thereof |
| CN103230781A (en) * | 2013-05-03 | 2013-08-07 | 重庆大学 | Heparin-phenylalanine adsorption material for blood purification method for removing endotoxin |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020092879A (en) * | 2018-12-13 | 2020-06-18 | 東レ株式会社 | Blood purification column |
| JP7230478B2 (en) | 2018-12-13 | 2023-03-01 | 東レ株式会社 | blood purification column |
| CN109692371A (en) * | 2019-01-28 | 2019-04-30 | 四川大学 | It is a kind of from anticoagulant double-layer active carbon blood perfusion device and blood perfusion method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105126787B (en) | 2017-06-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH0567305B2 (en) | ||
| Yan et al. | Different chemical groups modification on the surface of chitosan nonwoven dressing and the hemostatic properties | |
| CN101836952B (en) | Ambroxol injection and preparation method thereof | |
| CN105770976B (en) | Dodecyl chitosan is preparing the application in bleeding-stopping dressing | |
| JPH09234317A (en) | Virus removing filter | |
| CN105126787A (en) | Method for improving anticoagulant activity of adsorbent | |
| Xu et al. | Self-anticoagulant sponge for whole blood auto-transfusion and its mechanism of coagulation factor inactivation | |
| CN103211774A (en) | Gabexate mesylate composition for injection and preparation method thereof | |
| BRPI0610339A2 (en) | method for preparing recovered bovine thrombin, and method for preparing a purified bovine thrombin composition | |
| CN103463614B (en) | A kind of Argatroban injection and preparation method thereof | |
| CN113600148A (en) | Heparin-modified chitosan/cellulose microsphere-based hemoperfusion adsorbent, preparation method and application thereof | |
| CN103191054A (en) | Heparin sodium tube sealing injection and preparation method thereof | |
| CN102977392A (en) | Preparation method of bacterial cellulose capable of removing endotoxin | |
| JP2004516888A (en) | How to detoxify carbohydrate-containing solutions | |
| CN102212129A (en) | Method for extracting human fibrinogen from component I through column chromatography | |
| CN107281096A (en) | A kind of liquid drugs injection containing Peramivir and preparation method thereof | |
| Aiach et al. | Low molecular weight (LMW) heparin derivatives in experimental extra-corporeal circulation (ECC) | |
| US20080177240A1 (en) | Pyrogen-Free Neurosurgical Sponges | |
| CN104624170B (en) | Adsorbent for treating gram bacterial infection and blood perfusion device | |
| FI62103B (en) | REQUIREMENTS FOR THE REQUIREMENT OF HEPARIN MED HOEG SPECIFIC ACTIVITIES | |
| CN107192778B (en) | Method for separating bacterial biofilm inhibiting components based on target protein affinity monolithic chromatographic column | |
| CN107281097A (en) | A kind of liquid drugs injection containing FCE-26743A and preparation method thereof | |
| Ahmad et al. | Effects of bolus dose and continuous infusion of tranexamic acid on blood loss after coronary artery bypass grafting | |
| WO2018159604A1 (en) | Heparin conjugate | |
| CN108872409A (en) | A kind of method of specified molecular weight separation purifying hyaluronic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |