CN105289546A - Preparation method of adsorbent special for heparin sodium - Google Patents
Preparation method of adsorbent special for heparin sodium Download PDFInfo
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- CN105289546A CN105289546A CN201510846371.6A CN201510846371A CN105289546A CN 105289546 A CN105289546 A CN 105289546A CN 201510846371 A CN201510846371 A CN 201510846371A CN 105289546 A CN105289546 A CN 105289546A
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- 229920000669 heparin Polymers 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000003463 adsorbent Substances 0.000 title claims abstract description 11
- 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 title abstract description 7
- 229960001008 heparin sodium Drugs 0.000 title abstract description 7
- WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000004088 foaming agent Substances 0.000 claims abstract description 6
- 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 31
- 239000011347 resin Substances 0.000 claims description 31
- 229920005989 resin Polymers 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 241001566735 Archon Species 0.000 claims description 23
- 239000012071 phase Substances 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 18
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000008346 aqueous phase Substances 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 13
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 12
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 238000010792 warming Methods 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 238000005576 amination reaction Methods 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 9
- -1 trifluoromethyl acrylate methyl esters Chemical class 0.000 claims description 9
- 238000007265 chloromethylation reaction Methods 0.000 claims description 8
- 239000000376 reactant Substances 0.000 claims description 8
- 239000011592 zinc chloride Substances 0.000 claims description 8
- 235000005074 zinc chloride Nutrition 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 229920000642 polymer Polymers 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 238000001291 vacuum drying Methods 0.000 claims description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 5
- 238000007664 blowing Methods 0.000 claims description 5
- 239000002270 dispersing agent Substances 0.000 claims description 5
- 238000007306 functionalization reaction Methods 0.000 claims description 5
- 238000010557 suspension polymerization reaction Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 239000003957 anion exchange resin Substances 0.000 claims description 4
- 229920006184 cellulose methylcellulose Polymers 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 238000009413 insulation Methods 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 2
- 239000003999 initiator Substances 0.000 claims description 2
- BWZVWVOEWUSVMS-UHFFFAOYSA-N n,n-dimethylmethanamine;methanol Chemical compound OC.CN(C)C BWZVWVOEWUSVMS-UHFFFAOYSA-N 0.000 claims description 2
- 150000002978 peroxides Chemical class 0.000 claims description 2
- KFDVPJUYSDEJTH-UHFFFAOYSA-N 4-ethenylpyridine Chemical compound C=CC1=CC=NC=C1 KFDVPJUYSDEJTH-UHFFFAOYSA-N 0.000 abstract 1
- 238000006116 polymerization reaction Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 9
- HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 description 8
- 229960002897 heparin Drugs 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 238000012710 chemistry, manufacturing and control Methods 0.000 description 3
- 238000003795 desorption Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 230000000322 hemodialysis Effects 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 241000446313 Lamella Species 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000011153 ceramic matrix composite Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 229920003020 cross-linked polyethylene Polymers 0.000 description 1
- 239000004703 cross-linked polyethylene Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 239000011265 semifinished product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
Landscapes
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention discloses a preparation method of an adsorbent special for heparin sodium. In polymerization, slight FPMMA and 0.1-0.5 part of 4-vinyl pyridine are introduced to be used as comonomers, and methyl isobutyl carbinol is used as a pore-foaming agent, so as to improve the mechanical strength of the adsorbent.
Description
Technical field
The present invention relates to a kind of method of adsorbent, particularly a kind of preparation method of liquaemin Special adsorbent.
Background technology
Heparin appear as the miracle that numerous Patients with Cardiovascular/Cerebrovascular Diseases creates life.Current heparin is in the world the most effectively and the maximum anticoagulation medicine of quantity, is mainly used in cardiovascular and cerebrovascular disease and hemodialysis, and wherein, it is unique effective specific medicament in hemodialysis.Clinical practice and research display, heparin, except having blood coagulation resisting function, also has other multiple biologically active and clinical applications, comprises effect for reducing blood fat, anti-middle film smooth muscle cell (SMC) hyperplasia, promotes the effects such as fibrinolysis.In addition, LMWHs is the antithrombotic medicine of a large class be processed into further as raw material by heparin bulk drug, there is clinical medicine purposes more widely, become the choice drug of disease such as treatment Acute Venous thrombus and acute coronary artery syndrome (angina pectoris, miocardial infarction) etc.
The separation-extraction technology of a CN201210378781 heparin sodium crude discloses a kind of separation-extraction technology of heparin sodium crude, comprise the pretreatment of casing mucous membrane, resin adsorption, desorption process, finally precipitate, oven dry obtains heparin sodium crude, it is characterized in that: described desorption processing procedure is: with clear water to the resin cleaning after absorption 2-3 time, be neutral to pH value of solution, resin is placed in container, add the sodium chloride solution of 0.5-1mol/l, stir at normal temperatures, mixing speed is 100-150r/min, and be aided with sonification medium liquaemin is got off from desorption resin, the invention has the advantages that: when resin elution, adopt the sodium chloride solution of low concentration to be aided with ultrasonic wave and a wash-out is carried out to resin, its liquaemin wash-out yield can reach more than 99%.
The production method of a CN96122971 resin specially adsorbing liquaemin, provides the production method that a kind of chlorinty is high, do not contain the resin specially adsorbing liquaemin of methyl alcohol.Technical characteristics is inserted in the reaction tower of 24 ± 1 DEG C by the crosslinked polyethylene of reactant gross weight 6 ~ 12%, and adverse current passes into the chloromethyl ether 2 hours of reactant gross weight 32-44%; In tower during temperature 44 ± 2 DEG C, point 10 hours continuous dropping zinc chloride of 5 ± 1 DEG C and the mixed liquor of chloromethyl ether, its chloromethyl ether is the 8-16% of reactant gross weight, and the weight ratio of zinc chloride and chloromethyl ether is 1: 2; Obtain chloromethylation ball semi-finished product and be washed to PH >=4, keep temperature 30 ± 2 DEG C in tower, divide the trimethylamine aqueous solution of 10 hours continuous dropwise reaction thing gross weight 32-52%, retrofit with hydrochloric acid and be washed to neutrality, obtain the resin that the inventive method is produced, this patent product chlorinty is high, and methyl alcohol amount of precipitation is little.
The shortcomings such as above patent and polymeric adsorbent that known technology uses are mainly common macroporous weakly basic anion exchange resin, and have adsorbing liquaemin ability all to a certain extent lower, mechanical strength is low, easy fragmentation, have influence on the normal operation of commercial plant.
Summary of the invention
The object of the invention is to: for the deficiencies in the prior art, propose a kind of preparation method of liquaemin Special adsorbent.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
A kind of preparation method of liquaemin Special adsorbent is provided, comprises the following steps:
(1) preparation of aqueous phase
By weight, in pressure reaction still, add 100 parts of pure water, 0.5-2 part organic chemistry dispersant, stir; Described chemical dispersant is selected from polyvinyl alcohol, gelatin or CMC.
(2) preparation of oil phase
By weight, by the styrene of 100 parts, 10-20 part divinylbenzene, 0.1-0.5 part trifluoromethyl acrylate methyl esters (FPMMA), 0.1-0.5 part: 4-vinylpridine, 0.5-2 part peroxide initiator, 10-40 part pore-foaming agent, pore-foaming agent is methyl isobutyl carbinol, stir, obtain oil phase;
(3) suspension polymerization
By step 2) oil-phase solution for preparing is added to step 1) in be equipped with and prepare in the reactor of aqueous phase, then from 70-100 DEG C of reaction 10-15h, after reaction terminates, reactant mixture through acetone extract, vacuum drying, obtained polymer Archon;
(4) functionalization
By polymer Archon obtained for step (3) according to the chloromethylation technique of known D201 anion exchange resin in the industry and Amination Technique, take quantitative resin Archon and put into reactor, add Archon quality 2-4 chloromethyl ether doubly; Archon quality 2 times of dichloroethanes, add the zinc chloride with Archon homogenous quantities, and are warming up to 30-50 DEG C, insulation 10-20 hours, terminate chloromethylation, carry out aminating reaction, first liquor abstraction during amination, add Archon quality 2-5 times trimethylamine aqueous solution, finally be warming up to 30-50 DEG C, insulation 5-20 hours, terminates reaction, washing blowing, obtained resin specially adsorbing liquaemin.Because existing Amination Technique all uses trimethylamine aqueous solution or HCI solution, instead of trimethylamine methanol solution, so there is not the problem of methyl alcohol polluted product.
Described chemical dispersant is selected from polyvinyl alcohol, gelatin or CMC.
Styrene, divinylbenzene, trifluoromethyl acrylate methyl esters (FPMMA), 4-vinylpridine, methyl isobutyl carbinol, chloromethyl ether, zinc chloride, trimethylamine aqueous solution are commercially available prod.
The present invention has following effect
1) method of the present invention uses methyl isobutyl carbinol to be pore-foaming agent, and the pore structure of its uniqueness is high to liquaemin molecular selectivity, thus has higher adsorption effect, and exchange capacity is large, wash-out is easy, physical and chemical performance is stable,
2) introducing of trifluoromethyl acrylate methyl esters (FPMMA), 4-vinylpridine monomer improves the mechanical strength of adsorbent, thus extends long service life.
2) remain without methyl alcohol in the preparation of this exchanger resin, effectively to the pollution of liquaemin, can obtain highly purified liquaemin by reduce engine solvent.
Detailed description of the invention
Following instance is only further illustrate the present invention, is not restriction the scope of protection of the invention.
Embodiment 1:
(1) preparation of aqueous phase
In 2000L reactor, add 1000Kg pure water, 5 parts of gelatin, stir;
(2) preparation of oil phase
By the styrene of 100Kg, 15Kg divinylbenzene, 0.2Kg trifluoromethyl acrylate methyl esters (FPMMA), 0.3Kg4-vinylpyridine, 0.8Kg peroxide benzoyl, 30Kg methyl isobutyl carbinol, stir, obtain oil phase;
(3) suspension polymerization
By step 2) oil-phase solution for preparing is added to step 1) in be equipped with and prepare in the reactor of aqueous phase, by step 2) oil-phase solution for preparing is added to step 1) in be equipped with and prepare in the reactor of aqueous phase, then from 80 DEG C of reaction 12h, after reaction terminates, reactant mixture is through acetone extract, vacuum drying, obtained polymer Archon;
(4) functionalization
Take 200Kg resin Archon and put into 2000L reactor, add the chloromethyl ether of Archon quality 700Kg, 400Kg dichloroethanes, the zinc chloride of 200Kg, and be warming up to 40 DEG C, be incubated 15 hours,, terminate chloromethylation, carry out aminating reaction, first liquor abstraction during amination, add 600Kg trimethylamine aqueous solution, be finally warming up to 40 DEG C,, be incubated 12 hours, terminate reaction, washing blowing, obtained resin specially adsorbing liquaemin.Obtained resin specially adsorbing liquaemin products obtained therefrom is numbered KR-1.
Embodiment 2
(1) preparation of aqueous phase
In 2000L reactor, add 1000Kg pure water, 10 parts of polyvinyl alcohol, stir;
(2) preparation of oil phase
By the styrene of 100Kg, 10Kg divinylbenzene, 0.1Kg trifluoromethyl acrylate methyl esters (FPMMA), 0.1Kg4-vinylpyridine, 0.5Kg peroxide benzoyl, 10Kg methyl isobutyl carbinol, stir, obtain oil phase;
(3) suspension polymerization
By step 2) oil-phase solution for preparing is added to step 1) in be equipped with and prepare in the reactor of aqueous phase, by step 2) oil-phase solution for preparing is added to step 1) in be equipped with and prepare in the reactor of aqueous phase, then from 100 DEG C of reaction 10h, after reaction terminates, reactant mixture is through acetone extract, vacuum drying, obtained polymer Archon;
(4) functionalization
Take 300Kg resin Archon and put into 1000L reactor, add the chloromethyl ether of Archon quality 600Kg, 600Kg dichloroethanes, the zinc chloride of 300Kg, and be warming up to 30 DEG C, be incubated 20 hours,, terminate chloromethylation, carry out aminating reaction, first liquor abstraction during amination, add 600Kg trimethylamine aqueous solution, be finally warming up to 30 DEG C,, be incubated 20 hours, terminate reaction, washing blowing, obtained resin specially adsorbing liquaemin.Obtained resin specially adsorbing liquaemin products obtained therefrom is numbered KR-2.
Embodiment 3
(1) preparation of aqueous phase
In 2000L reactor, add 1000Kg pure water, 20 parts of CMCs, stir;
(2) preparation of oil phase
By the styrene of 100Kg, 20Kg divinylbenzene, 0.5Kg trifluoromethyl acrylate methyl esters (FPMMA), 0.5Kg4-vinylpyridine, 2Kg peroxide benzoyl, 40Kg methyl isobutyl carbinol, stir, obtain oil phase;
(3) suspension polymerization
By step 2) oil-phase solution for preparing is added to step 1) in be equipped with and prepare in the reactor of aqueous phase, by step 2) oil-phase solution for preparing is added to step 1) in be equipped with and prepare in the reactor of aqueous phase, then from 70 DEG C of reaction 15h, after reaction terminates, reactant mixture is through acetone extract, vacuum drying, obtained polymer Archon;
(4) functionalization
Take 100Kg resin Archon and put into 2000L reactor, add the chloromethyl ether of Archon quality 400Kg, 200Kg dichloroethanes, the zinc chloride of 100Kg, and be warming up to 50 DEG C, be incubated 10 hours,, terminate chloromethylation, carry out aminating reaction, first liquor abstraction during amination, add 500Kg trimethylamine aqueous solution, be finally warming up to 50 DEG C,, be incubated 5 hours, terminate reaction, washing blowing, obtained resin specially adsorbing liquaemin.Obtained resin specially adsorbing liquaemin products obtained therefrom is numbered KR-3.
Comparative example 1
Trifluoromethyl acrylate methyl esters (FPMMA) is not added, the other the same as in Example 1 in step 2.Products obtained therefrom is numbered KR-4.
Comparative example 2
4-vinylpridine is not added, the other the same as in Example 1 in step 2.Products obtained therefrom is numbered KR-5.
Comparative example 3
In step 1, methyl isobutyl carbinol is changed to toluene, the other the same as in Example 1.Products obtained therefrom is numbered KR-6.
Embodiment 7. resin treatment effect assessment, in table 1:
First enzyme-extracting solution is cooled to room temperature, carefully skim the grease lamella floating on liquid level, control is warming up to 45 degree, stop heating, under agitation add the resin that prior pretreatment good embodiment 1-3 and comparative example 1-3 is obtained, effectively adsorb the liquaemin composition in feed liquid, the consumption of new resin is 3% of feed liquid, should strengthen its consumption as one sees fit with regenerating resin later, stirring, adsorption treatment leave standstill after 3 hours and filter, and filtrate can be used as the raw material of the new drug arklemin of production for treating coronary heart disease.By the above-mentioned resin being adsorbed with heparin compositions first with the abundant rinsing of clear water, after clean, then with the 1.2mol/L sodium chloride solution of a times, liquaemin operation is carried out to the resin washed: elution time is 1 hour.Be filtered dry resin, eluent is merged.The eluent of above-mentioned gained is adjusted to PH=10, stirs after 30 minutes, leave standstill, then careful precipitation supernatant liquor, the suction filtration that bottom sediment is tried one's best is to dry.Merge clear liquid and filtrate, add alcohol settling and spend the night, next day, carefully dry sucking-off supernatant liquor, collect bottom sediment, suction filtration, to dry, through vacuum drying, obtain heparin sodium crude, then obtains refined heparin sodium through refining steps such as static filtrations.Calculate the maximum exchange amount % to heparin after the patent sample Reusability made of different process 300 times, and compare with D201 macroporous strong basic anion exchange resin
Table 1: the maximum exchange amount %. to liquaemin after product Reusability 100 times in embodiment
| Numbering | Heparin yield u/g wet resin | Rate of small round spheres % after mill |
| KR-1 | 2770 | 97 |
| KR-2 | 2682 | 97 |
| KR-3 | 2930 | 98 |
| KR-4 | 2320 | 95 |
| KR-5 | 2190 | 93 |
| KR-6 | 2455 | 90 |
| D201 | 1276 | 58 |
Claims (1)
1. a preparation method for liquaemin Special adsorbent, is characterized in that, described preparation method comprises the following steps:
(1) preparation of aqueous phase
By weight, in pressure reaction still, add 100 parts of pure water, 0.5-2 part organic chemistry dispersant, stir; Described chemical dispersant is selected from polyvinyl alcohol, gelatin or CMC;
(2) preparation of oil phase
By weight, by the styrene of 100 parts, 10-20 part divinylbenzene, 0.1-0.5 part trifluoromethyl acrylate methyl esters (FPMMA), 0.1-0.5 part: 4-vinylpridine, 0.5-2 part peroxide initiator, 10-40 part pore-foaming agent, pore-foaming agent is methyl isobutyl carbinol, stir, obtain oil phase;
(3) suspension polymerization
By step 2) oil-phase solution for preparing is added to step 1) in be equipped with and prepare in the reactor of aqueous phase, then from 70-100 DEG C of reaction 10-15h, after reaction terminates, reactant mixture through acetone extract, vacuum drying, obtained polymer Archon;
(4) functionalization
By polymer Archon obtained for step (3) according to the chloromethylation technique of known D201 anion exchange resin in the industry and Amination Technique, take quantitative resin Archon and put into reactor, add Archon quality 2-4 chloromethyl ether doubly; Archon quality 2 times of dichloroethanes, add the zinc chloride with Archon homogenous quantities, and are warming up to 30-50 DEG C, insulation 10-20 hours, terminate chloromethylation, carry out aminating reaction, first liquor abstraction during amination, add Archon quality 2-5 times trimethylamine aqueous solution, finally be warming up to 30-50 DEG C, insulation 5-20 hours, terminates reaction, washing blowing, obtained resin specially adsorbing liquaemin.Because existing Amination Technique all uses trimethylamine aqueous solution or HCI solution, instead of trimethylamine methanol solution, so there is not the problem of methyl alcohol polluted product.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646801A (en) * | 2016-03-09 | 2016-06-08 | 张玲 | Preparation of octylphenol ethoxylate adsorbing material |
| CN105859938A (en) * | 2016-06-13 | 2016-08-17 | 王金明 | Preparation of cobalt adsorbent |
| CN111939882A (en) * | 2020-09-03 | 2020-11-17 | 昌果生物医药科技河北有限公司 | Method for preparing adsorption resin by using chloroacetyl chloride and application of method in bilirubin adsorption |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101701054A (en) * | 2009-12-01 | 2010-05-05 | 福州大学 | Surface decorating method of porous polymer microspheres |
| CN103464222A (en) * | 2013-09-25 | 2013-12-25 | 凯瑞化工股份有限公司 | Preparation method of special anion exchange resin for adsorbing heparin sodium |
| CN103772575A (en) * | 2014-01-22 | 2014-05-07 | 王金明 | Method for preparing parting material for extracting lithium |
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| CN101701054A (en) * | 2009-12-01 | 2010-05-05 | 福州大学 | Surface decorating method of porous polymer microspheres |
| CN103464222A (en) * | 2013-09-25 | 2013-12-25 | 凯瑞化工股份有限公司 | Preparation method of special anion exchange resin for adsorbing heparin sodium |
| CN103772575A (en) * | 2014-01-22 | 2014-05-07 | 王金明 | Method for preparing parting material for extracting lithium |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646801A (en) * | 2016-03-09 | 2016-06-08 | 张玲 | Preparation of octylphenol ethoxylate adsorbing material |
| CN105859938A (en) * | 2016-06-13 | 2016-08-17 | 王金明 | Preparation of cobalt adsorbent |
| CN111939882A (en) * | 2020-09-03 | 2020-11-17 | 昌果生物医药科技河北有限公司 | Method for preparing adsorption resin by using chloroacetyl chloride and application of method in bilirubin adsorption |
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