CN109847809A - The device and its application method of the impurity such as protein and nucleic acid in a kind of removal crude heparin sodium - Google Patents
The device and its application method of the impurity such as protein and nucleic acid in a kind of removal crude heparin sodium Download PDFInfo
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- CN109847809A CN109847809A CN201811620177.6A CN201811620177A CN109847809A CN 109847809 A CN109847809 A CN 109847809A CN 201811620177 A CN201811620177 A CN 201811620177A CN 109847809 A CN109847809 A CN 109847809A
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- valve
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- ion exchange
- exchange column
- resin
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- 229920000669 heparin Polymers 0.000 title claims abstract description 52
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 31
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 31
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 28
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 25
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 25
- 239000012535 impurity Substances 0.000 title claims abstract description 21
- 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 claims abstract description 20
- 229960001008 heparin sodium Drugs 0.000 title claims abstract description 20
- 239000011347 resin Substances 0.000 claims abstract description 54
- 229920005989 resin Polymers 0.000 claims abstract description 54
- 238000005342 ion exchange Methods 0.000 claims abstract description 49
- 239000007788 liquid Substances 0.000 claims abstract description 36
- 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 32
- 229960002897 heparin Drugs 0.000 claims abstract description 32
- 239000002699 waste material Substances 0.000 claims abstract description 13
- 239000012043 crude product Substances 0.000 claims abstract description 11
- 238000003860 storage Methods 0.000 claims abstract description 11
- 239000000463 material Substances 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 30
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 26
- 239000011780 sodium chloride Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 238000002835 absorbance Methods 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 238000001179 sorption measurement Methods 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- 210000002381 plasma Anatomy 0.000 claims description 7
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 6
- 241000009298 Trigla lyra Species 0.000 claims description 6
- 239000003456 ion exchange resin Substances 0.000 claims description 6
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- 238000005422 blasting Methods 0.000 claims description 2
- 238000011010 flushing procedure Methods 0.000 claims description 2
- 238000001514 detection method Methods 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 239000012530 fluid Substances 0.000 description 7
- 238000005096 rolling process Methods 0.000 description 4
- 241001494479 Pecora Species 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Landscapes
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The invention discloses the devices and its application method of the impurity such as protein and nucleic acid in a kind of removal crude product heparin, it is characterized in that ion exchange column outlet at bottom is divided into three tunnels after threeway, connect after shut-off valve with collection liquid storage tank all the way, another way connects after shut-off valve with air compressor machine outlet, and third road connects after shut-off valve with waste liquid pool；Ion exchange column top is provided with three road entrances, connects after shut-off valve with vacuum pump all the way, successively connects by the road with after shut-off valve with material outlet all the way, and third road connects after shut-off valve with resin storage tank；Rhabodoid is installed in pipeline, rhabodoid upper end and ring flange are connected, and lower end and mono- plate body of are connected, and are installed with gap between plate body and pipeline lower port.The present invention improves the utilization rate of resin, reduces heparin loss, improves yield, ensure that the impurity removal effect such as protein and nucleic acid.The present invention produces choice goods heparin sodium detection protein content≤0.06%, is far below USP standard, refined heparin sodium titer yield can reach 98% or more.
Description
Technical field
The present invention relates to the devices and its application method of the impurity such as protein and nucleic acid in removable crude heparin sodium.
Background technique
It is mostly to be washed by ion exchange resin absorption heparin, salt in existing crude heparin sodium preparation refined heparin sodium technique
Deresination reaches the impurity such as isolating protein and nucleic acid, thus the purpose of purified heparin.But protein and nucleic acid removal effect
Fruit is limited, and the adsorption rate of ion exchange resin and eluting rate be frequently not it is very high, cause heparin yield relatively low.Wherein there are several points
Major defect leads to this problem.The first, the gap formed between resin vial wall and resin: when solution pastes tube wall flowing, by
The gap formed between tube wall and resin is larger, and the heparin that only fewer parts is contacted with resin can be adsorbed, to resin
After adsorption site saturation, resin no longer plays suction-operated, and more medical fluids flow out in gap, causes heparin loss；The second,
Be unevenly distributed inside resin: solution is easier to flow through gap larger part, after the saturation of gap larger part resin adsorption site, tree
Rouge no longer plays suction-operated, and the medical fluid flowed through herein is expelled directly out, and causes heparin loss；And most resin is due to inorganic
Medical fluid can be contacted, suction-operated can not be played, resulted in waste of resources；When third, solution flow through ion exchange column gap larger part,
Lasting wash away can expand voidage more liquid is caused to flow directly out without resin adsorption；4th, due to crude product heparin
It is needed before reaching ion-exchange process through supersalt solution, heat in medical fluid containing impurity, preparation processes such as a large amount of protein and nucleic acid
The techniques such as denaturation separate protein and nucleic acid from structure with heparin, coexist in a solution system, medical fluid is at this time
Viscous pasty state, in ion exchange, the same resin face of medical fluid continuous contact easily causes resin face to block and then can not flow；
The above problem directly affects the yield of heparin and goes the effect of the impurity such as isolating protein and nucleic acid.
Summary of the invention
The present invention provides the device and its application method of the impurity such as protein and nucleic acid in a kind of removable crude heparin sodium,
It is of the existing technology to solve the problems, such as.
The technical scheme adopted by the invention is as follows: the dress of the impurity such as protein and nucleic acid in this removal crude heparin sodium
It sets, it includes ion exchange column (7), it is characterised in that ion exchange column (7) outlet at bottom is divided into three tunnels after threeway,
In all the way after shut-off valve (2) with collect liquid storage tank (1) connect, another way after shut-off valve (3) with air compressor machine (5) export phase
It connects, third road connects after shut-off valve (4) with waste liquid pool (6)；Three road entrances are provided at the top of the ion exchange column (7),
In connect after shut-off valve (8) with vacuum pump (9) all the way, successively (12) and shut-off valve (10) go out with raw material another way afterwards by the road
Mouth connects, and third road connects after shut-off valve (15) with resin storage tank (14) outlet；A rhabodoid is installed in the pipeline (12)
(13), the upper end Yu ring flange (17) of the rhabodoid (13) are connected, and the lower end of rhabodoid (13) and mono- plate body of (11) are solid
Even, gap is installed between the plate body (11) and pipeline (12) lower port.
The application method of the device of the impurity such as protein and nucleic acid in the removal crude heparin sodium, it is characterised in that packet
Include following steps:
A. it is successively first opened after closing shut-off valve (2), shut-off valve (3), shut-off valve (4), shut-off valve (10) and shut-off valve (15)
Shut-off valve (8), the vacuum pump (9) of shut-off valve (8) control piper end connection at this time is interior to ion exchange column (7) to extract vacuum, when
Opening stop valve (15) injection ion into ion exchange column (7) is handed over when ion exchange column (7) interior vacuum degree reaches -0.08Mpa
The mixture for changing resin and water is then turned on shut-off valve (4), and part water is discharged to waste liquid pool (6)；
B. when the mixing object amount of the interior ion exchange resin of ion exchange column (7) and water is abundant, shut-off valve (2) is successively closed, are cut
Only valve (3), shut-off valve (4), shut-off valve (15) and shut-off valve (10), are then turned on shut-off valve (8), and shut-off valve (8) controls at this time
Emptying；When ion exchange column (7) external and internal pressure is identical, opening stop valve (2), when the water level in ion exchange column (7) is high
Degree with resin (16) interfacial level when flushing, opening stop valve (10) so that crude product heparin reaction solution by the road (12) inject from
In sub- exchange column (7)；When the outflow flow velocity by shut-off valve (2) has downward trend, shut-off valve (2) and shut-off valve are closed
(10), it is then turned on shut-off valve (3) and persistently blasts compressed air into ion exchange column (7), close shut-off valve (3) after 2 hours,
Successively opening stop valve (2) and shut-off valve (10) continue to adsorb again；
C. the step of repeating the above b, until crude product heparin reaction solution is all through resin adsorption；
D. confirm that shut-off valve (2), shut-off valve (3), shut-off valve (4), shut-off valve (15) and shut-off valve (10) are in off state, cut
After only valve (8) is open state, opening stop valve (10) makes low concentration sodium chloride solution (12) injection ion exchange column by the road
(7) start to wash resin (16) in, being then then turned on shut-off valve (4) makes waste liquid outflow enter waste liquid pool (6)；Pass through shut-off valve
(10) and the exit velocity of shut-off valve (4) suitable control shut-off valve (4)；This stage is the impurity such as protein and nucleic acid removal rank
Section, continues to be adsorbed on resin (16), to realize purifying without will affect heparin；
E. in the every 4 ± 0.5%(W/V that 4000L is added of washing resin stage) sodium chloride solution, it closes shut-off valve (4) and ends
Valve (10), opening stop valve (3), then to after persistently blasting compressed air 1 hour in ion exchange column (7), close shut-off valve
(3), then successively opening stop valve (4) and shut-off valve (10) again, take efflux to be measured with ultraviolet-uisible spectrophotometer；
F. the process for repeating above step d to e, until the liquid absorbance being discharged by shut-off valve (4) is qualified；
G. confirm that shut-off valve (2), shut-off valve (3), shut-off valve (4), shut-off valve (15) and shut-off valve (10) are to close and end
Valve (8) be open state after, first opening stop valve (10) makes 12 ± 0.5%(W/V) sodium chloride solution by the road (12) inject from
Sub- exchange column (7) wash-in deresination, being then then turned on shut-off valve (2) flows out liquid into collection liquid storage tank through shut-off valve (2)
(1)；
H. efflux blood plasma method is taken to survey potency in shut-off valve (2) outlet.After meeting the requirements, it can stop entering in next step.
The technological progress achieved by the present invention:
1. connecing resin sufficiently with heparin reaction solution due to the method in absorption phase using blow compressed air rolling resin
Touching, avoids reaction solution and is directly flowing through big gap, improve the utilization rate of resin, reduce heparin loss, improve receipts
Rate.In addition auxiliary measures efflux potency method using sheep blood plasma method, so that the risk of heparin loss is preferably minimized, in high yield
It provides and guarantees.
2. in the washing stage using the method for blow compressed air rolling resin, so that resin and low concentration sodium chloride solution
It comes into full contact with, realizes that chloride ion and protein and nucleic acid carry out ion exchange to greatest extent, so that protein and nucleic acid to the greatest extent may be used
It separates, is flowed out with sodium chloride solution, to realize protein and nucleic acid and heparin from a solution body on the slave resin of energy
It is separated in system, has achieved the purpose that purified heparin；In addition auxiliary is inhaled using ultraviolet-visible spectrophotometry detection efflux 260nm
Luminosity, it is desirable that≤0.200, it ensure that the effect of the impurity such as protein and nucleic acid removal.
3. the lower end of rhabodoid and mono- plate body of are connected, and plate body and pipeline due to installing a rhabodoid in pipeline
The structure in gap is installed between lower port, which can guarantee that the liquid that top pipeline enters enters in cylinder in umbrella point
Cloth and it is more uniform be distributed on resin face, increase the contact area of liquid and resin, avoid big moving liquid and directly rush
Brush causes the recess in resin face on resin face, in turn results in liquid and shortcut is selected to flow and reduce resin utilization rate in cylinder
The drawbacks of.
4. saving human cost due to filling resin in ion exchange column cylinder by the way of vacuum feeding, being more suitable for
It commercially produces.
5. refined heparin sodium produced by the invention, protein and nucleic acid content are well below statutory standard: European medicine
Allusion quotation specified protein content≤0.5%, absorbance≤0.15 nucleic acid 260nm, refined heparin sodium produced by the invention press European Pharmacopoeia
Method detects protein content≤0.1%, and absorbance≤0.09 nucleic acid 260nm is far below European Pharmacopoeia standard；United States Pharmacopeia rule
Determine protein content≤0.1%, nucleic acid content≤0.1%, the present invention produces choice goods heparin sodium by USP Method detection albumen
Matter content≤0.06%, nucleic acid impurities are not detected, and are far below USP standard, and the present invention produces choice goods titer of heparin sodium yield
It can reach 98% or more.
Detailed description of the invention
Fig. 1 is schematic structural view of the invention.
Fig. 2 is the portion the A enlarged structure schematic diagram of Fig. 1.
Specific embodiment
With reference to the accompanying drawing with the invention will be further described.
As shown in Figure 1 and Figure 2, it is this removal crude heparin sodium in the impurity such as protein and nucleic acid device it include ion
The outlet at bottom of exchange column 7, the ion exchange column 7 is divided into three tunnels after threeway, wherein all the way after shut-off valve 2 with collection liquid
1 entrance of storage tank connects, and another way connects after shut-off valve 3 with the outlet of air compressor machine 5, and third road is followed by waste liquid pool 6 through shut-off valve 4；
Three road entrances are provided at the top of ion exchange column 7, wherein connecting after shut-off valve 8 with the outlet of vacuum pump 9 all the way, another way is successively
By the road 12 and shut-off valve 10 after be divided into two-way, wherein connecting all the way with crude product medical fluid material outlet, another way is molten with sodium chloride
Liquid material outlet connects, and third road is followed by resin storage tank 14 through shut-off valve 15 and exports；A rhabodoid 13, the bar are installed in pipeline 12
The upper end of shape body 13 and ring flange 17 are connected, and aperture passes through in order to material liquid on ring flange 17, the lower end of rhabodoid 13 and mono-
Plate body 11 is connected, which has a diameter larger than the outer diameter of pipeline 12, between 12 lower port of plate body 11 and pipeline
It is installed with gap, in order to be uniformly distributed in ion exchange column 7 in umbrella in the liquid that the gap is flowed out.
In this removable crude heparin sodium of the present invention application method of the device of the impurity such as protein and nucleic acid include with
Lower step:
A. after successively closing shut-off valve 2, shut-off valve 3, shut-off valve 4, shut-off valve and 10 shut-off valves 15, first opening stop valve 8, this
When 8 control piper end of shut-off valve connection vacuum pump 9, to vacuum is extracted in ion exchange column 7, when vacuum in ion exchange column 7
Degree opening stop valve 15 when reaching -0.08Mpa, due to being vacuum state in ion exchange column 7, ion exchange resin and water at this time
Mixture through resin storage tank 14 by shut-off valve 15 flow into ion exchange column 7 in, realize vacuum holding resin；It is then turned on cut-off
Part water is discharged to waste liquid pool 6, resin and aqueous mixtures can be made persistently to sink in this way by valve 4.
B. it when the mixing object amount of ion exchange resin in ion exchange column 7 and water is abundant, successively closes shut-off valve 2, cut
Only valve 3, shut-off valve 4, shut-off valve 15 and shut-off valve 10, are then turned on shut-off valve 8, and 8 control piper of shut-off valve outlet at this time is to open
State is put, emptying is played；When 7 external and internal pressure of ion exchange column is identical, opening stop valve 2, at this time in ion exchange column 7
Water by 2 control piper of shut-off valve enter collect liquid storage tank 1, in ion exchange column 7 water level height and 16 boundary of resin
When face height flushes, opening stop valve 10, so that crude product heparin reaction solution by the road work as in ion exchange column 7 by 12 injections, due to
The barrier effect of circular plate body 11, by the road 12 enter ion exchange columns 7 in crude product heparin reaction solution plate body 11 with
Gap location between 12 lower port of pipeline is uniformly distributed in umbrella into ion exchange column 7 when flowing out, and ensure that heparin reacts
Liquid with resin surface is more uniform contacts；By controlling the flow velocity of shut-off valve 2 and 10 2.7 ~ 3.0L/min of suitable control of shut-off valve, to
It was found that closing shut-off valve 2 and shut-off valve 10 when the outflow flow velocity by shut-off valve 2 has downward trend, being then turned on shut-off valve
3, compressed air is persistently blasted into ion exchange column 7 by air compressor machine 5 at this time, turns over crude product heparin solution and resin 16 sufficiently
Rolling closes shut-off valve 3, then successively opening stop valve 2 and shut-off valve 10, continues to adsorb after 2 hours；
C. the step of repeating above a to the b, until crude product heparin reaction solution is all through resin adsorption；Blood plasma method is used in adsorption process
Potency is surveyed, method is to take 210 μ l of efflux, and 1ml sheep blood plasma is added, 0.8ml0.25% calcium chloride solution is added, shakes up, 30 minutes
It is interior to solidify, illustrate all to be adsorbed on resin 16 through no-rod tractor, i.e. heparin in 1 control piper efflux of shut-off valve, guarantee
Heparin yield；
D. confirm that shut-off valve 2, shut-off valve 3, shut-off valve 4, shut-off valve 15 and shut-off valve 10 are in off state, shut-off valve 8 is unlatching
After state, opening stop valve 10 makes 4 ± 0.5%(W/V) sodium chloride solution by the road 12 injection ion exchange columns 7 in start to wash
Resin 16, being then then turned on shut-off valve 4 flows out liquid by the road into waste liquid pool 6；It is appropriate by shut-off valve 10 and shut-off valve 4
Control the exit velocity of shut-off valve 4；This stage is the impurity such as the protein and nucleic acid removal stage, is continued without will affect heparin
It is adsorbed on resin 16, to realize purifying；
E. in the every 4 ± 0.5%(W/V that 4000L is added of washing resin stage) sodium chloride solution, close shut-off valve 4 and shut-off valve
10, opening stop valve 3 persistently blasts compressed air 1 hour into ion exchange column 7, with heparin solution and the resin of sufficiently rolling
16, shut-off valve 3 is turned off, successively opening stop valve 4 and shut-off valve 10, take appropriate efflux to be surveyed with ultraviolet-uisible spectrophotometer
Determine 260nm absorbance, it is desirable that absorbance≤0.200 260nm；
F. the process of above step d to e is repeated, until 4 ± 0.5%(W/V of 30000L is added) after sodium chloride solution, by section
The liquid that only valve 4 is discharged is 0.013 through detection efflux 260nm absorbance, is met the requirements into next step；
G. after the liquid absorbance that shut-off valve 4 is discharged is qualified, confirm shut-off valve 2, shut-off valve 3, shut-off valve 4,15 and of shut-off valve
Shut-off valve 10 is to close and after shut-off valve 8 is open state, first opening stop valve 10 makes 12 ± 0.5(W/V) sodium chloride solution
12 injection 7 wash-in deresination of ion exchange column by the road, being then then turned on shut-off valve 2 makes liquid flow out and collect through shut-off valve 2
Liquid；It is 2.7 ~ 3.0L/min by shut-off valve 10 and 2 coutroi velocity of shut-off valve, so that the heparin elution being adsorbed on resin 16
Get off；
H. it takes shut-off valve 2 to export efflux blood plasma method and surveys potency, take 210 μ l of efflux, 1ml sheep blood plasma is added, be added
0.8ml0.25% calcium chloride solution, shakes up, if stopping elution when coagulating entirely in 30 minutes, collects solution and carries out next step operation.
The refined heparin sodium for using above method to prepare by European Pharmacopoeia standard detection protein content for 0.05%, nucleic acid
260nm absorbance is 0.07；It is 0.04% by USP standard detection protein content, nucleic acid impurities are not detected.This batch of heparin
Sodium titer yield is 99.5%.
Claims (2)
1. the device of the impurity such as protein and nucleic acid in a kind of removal crude heparin sodium, it includes ion exchange column (7), feature
It is that the ion exchange column (7) outlet at bottom is divided into three tunnels after threeway, wherein storing up after shut-off valve (2) with collection liquid all the way
Tank (1) connects, and another way connects after shut-off valve (3) with air compressor machine (5) outlet, and third road is after shut-off valve (4) and waste liquid pool
(6) connect；Be provided with three road entrances at the top of the ion exchange column (7), wherein all the way after shut-off valve (8) with vacuum pump (9)
Connect, successively (12) and shut-off valve (10) connect with material outlet another way afterwards by the road, third road after shut-off valve (15) with
Resin storage tank (14) outlet connects；A rhabodoid (13) are installed in the pipeline (12), the upper end of the rhabodoid (13) and method
Blue disk (17) is connected, and the lower end of rhabodoid (13) and mono- plate body of (11) are connected, the plate body (11) and pipeline (12) lower end
Gap is installed between mouthful.
2. the application method of the device of the impurity such as protein and nucleic acid in removal crude heparin sodium according to claim 1,
Characterized by the following steps:
A. it is successively first opened after closing shut-off valve (2), shut-off valve (3), shut-off valve (4), shut-off valve (10) and shut-off valve (15)
Shut-off valve (8), the vacuum pump (9) of shut-off valve (8) control piper end connection at this time is interior to ion exchange column (7) to extract vacuum, when
Opening stop valve (15) injection ion into ion exchange column (7) is handed over when ion exchange column (7) interior vacuum degree reaches -0.08Mpa
The mixture for changing resin and water is then turned on shut-off valve (4), and part water is discharged to waste liquid pool (6)；
B. when the mixing object amount of the interior ion exchange resin of ion exchange column (7) and water is abundant, shut-off valve (2) is successively closed, are cut
Only valve (3), shut-off valve (4), shut-off valve (15) and shut-off valve (10), are then turned on shut-off valve (8), and shut-off valve (8) controls at this time
Emptying；When ion exchange column (7) external and internal pressure is identical, opening stop valve (2), when the water level in ion exchange column (7) is high
Degree with resin (16) interfacial level when flushing, opening stop valve (10) so that crude product heparin reaction solution by the road (12) inject from
In sub- exchange column (7)；When the outflow flow velocity by shut-off valve (2) has downward trend, shut-off valve (2) and shut-off valve are closed
(10), it is then turned on shut-off valve (3) and persistently blasts compressed air into ion exchange column (7), close shut-off valve (3) after 2 hours,
Successively opening stop valve (2) and shut-off valve (10) continue to adsorb again；
C. the step of repeating the above b, until crude product heparin reaction solution is all through resin adsorption；
D. confirm that shut-off valve (2), shut-off valve (3), shut-off valve (4), shut-off valve (15) and shut-off valve (10) are in off state, cut
After only valve (8) is open state, opening stop valve (10) makes low concentration sodium chloride solution (12) injection ion exchange column by the road
(7) start to wash resin (16) in, being then then turned on shut-off valve (4) makes waste liquid outflow enter waste liquid pool (6)；Pass through shut-off valve
(10) and the exit velocity of shut-off valve (4) suitable control shut-off valve (4)；This stage is the impurity such as protein and nucleic acid removal rank
Section, continues to be adsorbed on resin (16), to realize purifying without will affect heparin；
E. in the every 4 ± 0.5%(W/V that 4000L is added of washing resin stage) sodium chloride solution, it closes shut-off valve (4) and ends
Valve (10), opening stop valve (3), then to after persistently blasting compressed air 1 hour in ion exchange column (7), close shut-off valve
(3), then successively opening stop valve (4) and shut-off valve (10) again, take efflux to be measured with ultraviolet-uisible spectrophotometer；
F. the process for repeating above step d to e, until the liquid absorbance being discharged by shut-off valve (4) is qualified；
G. confirm that shut-off valve (2), shut-off valve (3), shut-off valve (4), shut-off valve (15) and shut-off valve (10) are to close and end
Valve (8) be open state after, first opening stop valve (10) makes 12 ± 0.5%(W/V) sodium chloride solution by the road (12) inject from
Sub- exchange column (7) wash-in deresination, being then then turned on shut-off valve (2) flows out liquid into collection liquid storage tank through shut-off valve (2)
(1)；
H. efflux blood plasma method is taken to survey potency in shut-off valve (2) outlet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811620177.6A CN109847809A (en) | 2018-12-28 | 2018-12-28 | The device and its application method of the impurity such as protein and nucleic acid in a kind of removal crude heparin sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811620177.6A CN109847809A (en) | 2018-12-28 | 2018-12-28 | The device and its application method of the impurity such as protein and nucleic acid in a kind of removal crude heparin sodium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109847809A true CN109847809A (en) | 2019-06-07 |
Family
ID=66892788
Family Applications (1)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115072924A (en) * | 2022-06-30 | 2022-09-20 | 金川集团股份有限公司 | Method for removing heavy ammonia nitrogen from cobalt carbonate industrial wastewater |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN202366713U (en) * | 2011-11-30 | 2012-08-08 | 河北瑞晶康生物科技有限公司 | Ion exchange column distributor |
| CN204380695U (en) * | 2014-12-31 | 2015-06-10 | 薛林 | A kind of environment measuring ion exchange column |
| CN106215983A (en) * | 2016-08-19 | 2016-12-14 | 山东万邦赛诺康生化制药股份有限公司 | The heparin sodium ion exchanger of air mixing and exchange method thereof |
| CN106422414A (en) * | 2016-11-11 | 2017-02-22 | 天津中医药大学 | Automatic-column-mounting continuous-operating in-series macroporous resin adsorption and separation device |
| CN106589167A (en) * | 2016-11-29 | 2017-04-26 | 重庆伊诺生化制品有限公司 | Preparation method of high-titer heparin sodium crude product and production apparatus therefor |
| CN107293343A (en) * | 2017-06-12 | 2017-10-24 | 航天晨光股份有限公司 | The loading and unloading transporter and its conveyer method of nuclear power station spent resin |
| CN108329405A (en) * | 2018-02-08 | 2018-07-27 | 黄石市典雅生物科技有限公司 | It is protected under a kind of resin adsorption state and the method for purified heparin sodium |
-
2018
- 2018-12-28 CN CN201811620177.6A patent/CN109847809A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN202366713U (en) * | 2011-11-30 | 2012-08-08 | 河北瑞晶康生物科技有限公司 | Ion exchange column distributor |
| CN204380695U (en) * | 2014-12-31 | 2015-06-10 | 薛林 | A kind of environment measuring ion exchange column |
| CN106215983A (en) * | 2016-08-19 | 2016-12-14 | 山东万邦赛诺康生化制药股份有限公司 | The heparin sodium ion exchanger of air mixing and exchange method thereof |
| CN106422414A (en) * | 2016-11-11 | 2017-02-22 | 天津中医药大学 | Automatic-column-mounting continuous-operating in-series macroporous resin adsorption and separation device |
| CN106589167A (en) * | 2016-11-29 | 2017-04-26 | 重庆伊诺生化制品有限公司 | Preparation method of high-titer heparin sodium crude product and production apparatus therefor |
| CN107293343A (en) * | 2017-06-12 | 2017-10-24 | 航天晨光股份有限公司 | The loading and unloading transporter and its conveyer method of nuclear power station spent resin |
| CN108329405A (en) * | 2018-02-08 | 2018-07-27 | 黄石市典雅生物科技有限公司 | It is protected under a kind of resin adsorption state and the method for purified heparin sodium |
Non-Patent Citations (1)
| Title |
|---|
| 张弓, 北京：化学工业出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115072924A (en) * | 2022-06-30 | 2022-09-20 | 金川集团股份有限公司 | Method for removing heavy ammonia nitrogen from cobalt carbonate industrial wastewater |
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Application publication date: 20190607 |