CN103936889A - Method for purification of enoxaparin by tangential flow filtration - Google Patents
Method for purification of enoxaparin by tangential flow filtration Download PDFInfo
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Abstract
The invention discloses a method for purification of enoxaparin by tangential flow filtration. The method comprises the steps of: a. preparation; b. parameter setting; c. setting of the flow rate of a pump; d. concentration; e. removal of low molecular weight impurities and salt; f. ultrafiltration; and g. index detection. The method for purification of enoxaparin by the tangential flow filtration (TFF) technology provided by the invention can be applied to desalination concentration purification of enoxaparin, the filtration retention volume can be small, the product yield can be high, and purification desalination concentration can be realized by one step. Being rapid, efficient and mild, the method shortens the operation time and operability, and reduces the cost. Through real-time process data recording, the scale can be enlarged from the research and development level to the production level directly, simply, stably and reliably.
Description
Technical field
The present invention relates to the field of enoxaparin, more specifically, the present invention relates to a kind of method of using tangential flow filtration purifying enoxaparin, be applied to the purifying of enoxaparin.
Background technology
Heparin sodium (Heparin) is the biologically active substance being extensively present in people and mammalian tissues, belong to natural mucopolysaccharide class, its chemical structure is alternately formed by connecting by D-glucose aldehydic acid and D-glucose amine, molecular weight distribution 5,000-30,000 dalton (molecular-weight average is 20,000 dalton).Heparin sodium is one of the most complicated organic compound of the known molecular structure of the mankind up to now.Heparin sodium has very strong anticoagulation, anti-thrombus function, i.e. anti-II a and anti-Xa function.Life-time service unfractionated heparin sodium has induced platelet to reduce the risk (3%) of disease, and thrombocytopenia can cause the increase of thrombosis and mortality ratio.
Enoxaparin Sodium (Enoxaparin Sodium) is one of Low molecular heparin class (low molecular weightheparin is called for short LMWH) kind, is mainly used in antithrombotic, anticoagulation, treatment acute myocardial infarction and unstable angina pectoris etc.Its anti-blood complicated mechanism, adaptability is more extensive, and the links of blood coagulation is had to effect, has market outlook widely.The at present production of enoxaparin mainly by heparin after cracking under alkaline condition, with organic solvent deposit, oven dry, dialysis/ultrafiltration, the means of purification such as freeze-drying obtain pharmaceutical grade enoxaparin.
Compare with unfractionated heparin sodium, " Enoxaparin Sodium " has similar anti-freezing usefulness, but cause that thrombocytopenic side effect obviously reduces, the plurality of advantages such as hemorrhage complication also reduces, subcutaneous injection good absorption, Half-life in vivo are long, share of market accounts for heparin series products more than 2/3.
Dialysis process in current Enoxaparin Sodium means of purification exists quantity of exchanged water large, and can not automatic operation, the dialysis operating time is long, amplification process poor operability, the high defects such as energy consumption height that cause of freeze-drying process water content, and the common ultra-filtration technique treatment capacity of using is at present restricted, not strong to amplification process data refer from laboratory stage, can not predict well that lab scale arrives pilot scale and the needed process parameter of scale production, thereby affect the quality control of whole production process.
Summary of the invention
The technical problem that the present invention mainly solves is to provide a kind of method of using tangential flow filtration purifying enoxaparin, application in the removal of impurities of enoxaparin desalination and concentration, make to filter hold-up volume little, product yield is high, one step realizes removal of impurities desalination and concentration, fast, efficiently gentle, shorten operating time and operability, reduce costs; By real-time process data, record to realize and direct, easyly reliablely and stablely from research and development scale, be amplified to industrial scale.
For solving the problems of the technologies described above, the technical scheme that the present invention adopts is: a kind of method of using tangential flow filtration purifying enoxaparin is provided, has comprised the following steps:
A, pre-preparation: enoxaparin sample dissolution, in pure water, is then filled to after constant volume and in port processing vessel, forms enoxaparin solution, and connect buffer container, place liquid header on osmotic balance, osmotic balance makes zero;
B, parameter setting: pressure monitor and pump, by the external computer of USB interface data line, carry out parameter setting by software in computer;
C, the flow velocity of pump is set: close through liquid port, disconnect port processing vessel and buffer container, open pump, by pump, from porthandler, extract enoxaparin solution, pipeline by film upper liquid outlet enters hollow fiber film assembly, pressure transmitter is by data feedback to pressure monitor, and the pipeline that enoxaparin solution enters film fluid port last time refluxes, in automatic back pressure valve backflow entry port processing vessel;
D, enriching stage: use computer to start image data, move and open through liquid port after 5 minutes, pump extracts enoxaparin solution from port processing vessel, pipeline by film upper liquid outlet enters hollow fiber film assembly, pressure transmitter by data feedback to pressure monitor, the small portion liquid of enoxaparin solution infiltrates in liquid header by the pipeline of infiltration mouth, most of liquid of enoxaparin solution flows in inbound port processing vessel by the back of pipeline of film fluid port last time, progressively improve TMP, the flow velocity that TMP changes the interior penetrating fluid of pipeline of infiltration mouth is set, enoxaparin solution enters enriching stage, low molecular impurity and salt are removed simultaneously,
E, remove low molecular impurity and salt: when enoxaparin solution is concentrated into after certain volume, in buffer container, add pure water, because tubing system is inner sealing state, while penetrating liquid in buffer container, port is processed internal tank and is formed vacuum, pure water in buffer container is sucked, enoxaparin solution enters constant volume and changes the liquid stage, realize removing of low molecular impurity and salt, realize and remove low-molecular polysaccharide and the distribution of Molecular regulator amount simultaneously, observe pressure and seepage discharge and change, regulation and control TMP changes seepage velocity;
F, complete ultrafiltration: by measuring salts contg in penetrating fluid, determine and change water multiple, when changing water and reach 4-8 times, enoxaparin solution completes ultrafiltration, disconnects buffer container, concentrated enoxaparin is to being difficult to have liquid to ooze, computer stops data gathering, and save data, closes pump, stop the experiment of enoxaparin ultrafiltration, cleaning equipment;
G, index detect: by the freeze-drying of enoxaparin heparin sample, take quality, and calculated yield, product index detects.
In a preferred embodiment of the present invention, described osmotic balance is connected with hollow fiber film assembly by seeing through liquid port, described hollow fiber film assembly is connected with pressure monitor with automatic back pressure valve respectively, described port processing vessel is connected between automatic back pressure valve and pressure monitor, described buffer container is connected with port processing vessel, described computer and pressure monitor are external, described liquid header is placed on above osmotic balance, and described pressure monitor is arranged on pump.
In a preferred embodiment of the present invention, the flow velocity 70-90ml/min of described pump, controls shearing force 2500 ~ 3500/s.
In a preferred embodiment of the present invention, described hollow fiber film assembly comprises hollow fiber membrane filter and ultra-filtration membrane, and described ultra-filtration membrane is arranged on hollow fiber membrane filter inside.
In a preferred embodiment of the present invention, described ultra-filtration membrane is modified poly (ether sulfone) film, molecular weight cut-off 1kD.
In a preferred embodiment of the present invention, on described hollow fiber membrane filter, be provided with three interfaces, comprise infiltration mouth, film upper liquid outlet and film fluid port last time, the middle side part that described infiltration mouth is arranged on hollow fiber membrane filter with see through liquid port and be connected, described film fluid port last time and film upper liquid outlet are arranged on respectively top and the bottom of hollow fiber membrane filter.
In a preferred embodiment of the present invention, described pressure transmitter comprises Pp pressure transmitter, Pr pressure transmitter and Pf pressure transmitter, described Pp pressure transmitter and Pf pressure transmitter are arranged on respectively the position of film upper liquid outlet and film fluid port last time, and described Pr pressure transmitter is arranged on the position of infiltration mouth.
The invention has the beneficial effects as follows: the method for use tangential flow filtration purifying enoxaparin of the present invention, application in the removal of impurities of enoxaparin desalination and concentration, make to filter hold-up volume little, product yield is high, one step realizes removal of impurities desalination and concentration, fast, efficiently gentle, shorten operating time and operability, reduce costs; By real-time process data, record to realize and direct, easyly reliablely and stablely from research and development scale, be amplified to industrial scale.
Accompanying drawing explanation
In order to be illustrated more clearly in the technical scheme in the embodiment of the present invention, below the accompanying drawing of required use during embodiment is described is briefly described, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skills, do not paying under the prerequisite of creative work, can also according to these accompanying drawings, obtain other accompanying drawing, wherein:
Fig. 1 is the schema of method one preferred embodiment of use ultrafiltration purification enoxaparin of the present invention;
Fig. 2 is the structured flowchart that the hyperfiltration process of enoxaparin is used equipment.
Embodiment
Below the technical scheme in the embodiment of the present invention is clearly and completely described, obviously, described embodiment is only a part of embodiment of the present invention, rather than whole embodiment.Embodiment based in the present invention, those of ordinary skills, not making all other embodiment that obtain under creative work prerequisite, belong to the scope of protection of the invention.
Refer to Fig. 1, the embodiment of the present invention comprises:
A method of using ultrafiltration purification enoxaparin, comprises the following steps:
A, pre-preparation: enoxaparin sample dissolution, in pure water, is then filled to after constant volume and in port processing vessel, forms enoxaparin solution, and connect buffer container, place liquid header on osmotic balance, osmotic balance makes zero;
B, parameter setting: pressure monitor and pump, by the external computer of USB interface data line, carry out parameter setting by software in computer;
C, the flow velocity of pump is set: close through liquid port, disconnect port processing vessel and buffer container, open pump, by pump, from porthandler, extract enoxaparin solution, pipeline by film upper liquid outlet enters hollow fiber film assembly, pressure transmitter is by data feedback to pressure monitor, and the pipeline that enoxaparin solution enters film fluid port last time refluxes, in automatic back pressure valve backflow entry port processing vessel;
D, enriching stage: use computer to start image data, move and open through liquid port after 5 minutes, pump extracts enoxaparin solution from port processing vessel, pipeline by film upper liquid outlet enters hollow fiber film assembly, pressure transmitter by data feedback to pressure monitor, the small portion liquid of enoxaparin solution infiltrates in liquid header by the pipeline of infiltration mouth, most of liquid of enoxaparin solution flows in inbound port processing vessel by the back of pipeline of film fluid port last time, progressively improve TMP, the flow velocity that TMP changes the interior penetrating fluid of pipeline of infiltration mouth is set, enoxaparin solution enters enriching stage, low molecular impurity and salt are removed simultaneously,
E, remove low molecular impurity and salt: when enoxaparin solution is concentrated into after certain volume, in buffer container, add pure water, because tubing system is inner sealing state, while penetrating liquid in buffer container, port is processed internal tank and is formed vacuum, pure water in buffer container is sucked, enoxaparin solution enters and changes the water stage, realize removing of low molecular impurity and salt, low-molecular polysaccharide is removed and the distribution of Molecular regulator amount simultaneously, observe pressure and seepage discharge and change, regulation and control TMP changes seepage velocity;
F, complete ultrafiltration: by measuring salts contg in penetrating fluid, determine and change water multiple, when changing water and reach 4-8 times, enoxaparin solution completes ultrafiltration, disconnects buffer container, concentrated enoxaparin is to being difficult to have liquid to ooze, computer stops data gathering, and save data, closes pump, stop the experiment of enoxaparin ultrafiltration, cleaning equipment;
G, index detect: by the freeze-drying of enoxaparin heparin sample, take quality, and calculated yield, product index detects.
In above-mentioned, the parameter setting in step b comprises:
1. date;
2. filter assemblies Part No., after input filtration Part No., comprises the filtering information input automatically of surface-area, approximate fibre count, staple length, shearing rate guide and film type;
3. sequence number;
4. the line size of proofreading and correct by pump head and pipeline, as: tubing size:14,
5. assembly form date.
Complete after ultrafiltration, need external a small amount of purified rinse water ultrafiltration pipeline and collect, then use purified rinse water ultrafiltration system, finally use 0.4% sodium hydroxide solution to clean ultra-filtration membrane, and moistening preservation.
Further, the flow velocity of described pump is 70-90ml/min, controls shearing force 2500 ~ 3500/s.
As shown in Figure 2, described osmotic balance is connected with hollow fiber film assembly by seeing through liquid port, described hollow fiber film assembly is connected with pressure monitor with automatic back pressure valve respectively, described port processing vessel is connected between automatic back pressure valve and pressure monitor, described buffer container is connected with port processing vessel, described computer and pressure monitor are external, and described liquid header is placed on above osmotic balance, and described pressure monitor is arranged on pump.
In the present invention, described hollow fiber film assembly comprises hollow fiber membrane filter and ultra-filtration membrane, and described ultra-filtration membrane is arranged on hollow fiber membrane filter inside.Wherein, described ultra-filtration membrane is modified poly (ether sulfone) film, molecular weight cut-off 1kD.
In above-mentioned, on described hollow fiber membrane filter, be provided with three interfaces, comprise infiltration mouth, film upper liquid outlet and film fluid port last time, the middle side part that described infiltration mouth is arranged on hollow fiber membrane filter is connected with infiltration pincers, and described film fluid port last time and film upper liquid outlet are arranged on respectively top and the bottom of hollow fiber membrane filter.
Further, described pressure transmitter comprises Pp pressure transmitter, Pr pressure transmitter and Pf pressure transmitter, described Pp pressure transmitter and Pf pressure transmitter are arranged on respectively the position of film upper liquid outlet and film fluid port last time, and described Pr pressure transmitter is arranged on the position of infiltration mouth.
Example one:
A, take enoxaparin 92mg and be dissolved in 10ml ultrapure water, constant volume, vibration evenly, is placed in port processing vessel, and connects buffer container, places liquid header on osmotic balance, and osmotic balance makes zero;
B, pressure monitor and peristaltic pump, by the external computer of USB interface data line, carry out parameter setting by software in computer, and selecting ultra-filtration membrane is 1kD, 115cm
2;
The flow velocity 70ml/min of c, setting peristaltic pump, shearing force 2648/s, closes through liquid port, disconnects port processing vessel and buffer container, opens peristaltic pump, and enoxaparin solution enters reflux pipeline on film and is back in port processing vessel;
D, use computer start image data, record, move and open through liquid port after 5 minutes, peristaltic pump extracts the small portion liquid in enoxaparin solution from port processing vessel, can infiltrate in liquid header by the pipeline of infiltration mouth, most of liquid flows in inbound port processing vessel by the back of pipeline of film fluid port last time, and enoxaparin solution enters enriching stage, low molecular impurity and salt is removed simultaneously;
E, automatic back pressure valve is adjusted to manual, carries out the setting of TMP pressure, progressively rise to 10;
F, when enoxaparin solution is concentrated into certain volume, in buffer container, add pure water, enoxaparin solution is carried out to desalination, except low-molecular polysaccharide, Molecular regulator amount distributes, while regulating TMP to 10, measuring ultrafiltration seepage velocity is 0.95ml/min; TMP is 12 o'clock, seepage velocity 1.05ml/min;
G, when changing water and reach 3.5 times, enoxaparin solution penetrating fluid is measured salt-free, disconnects buffer container, concentrated enoxaparin is to being difficult to have liquid to ooze, computer stops data gathering, save data, closes peristaltic pump, stops the experiment of enoxaparin ultrafiltration.Freeze-drying enoxaparin product obtains 79mg, and product is qualified.
Example two:
A, take enoxaparin 98mg and be dissolved in 10ml ultrapure water, constant volume, vibration evenly, is placed in port processing vessel, and connects buffer container, places liquid header on osmotic balance, and osmotic balance makes zero;
B, pressure monitor and peristaltic pump, by the external computer of USB interface data line, carry out parameter setting by software in computer, and selecting ultra-filtration membrane is 1kD, 115cm
2;
The flow velocity 80ml/min of c, setting peristaltic pump, shearing force 3018/s, closes through liquid port, disconnects port processing vessel and buffer container, opens peristaltic pump;
D, computer start image data, are now the total reflux stage, move after 5 minutes and open through liquid port;
E, TMP is set is 8.0, peristaltic pump extracts enoxaparin solution from port processing vessel, small portion infiltrates in liquid header, in most of backflow entry port processing vessel, enoxaparin solution enters enriching stage, and measuring now Pf is 8.1psi, Pp is-0.4psi, Pr is 7.3psi, and TMP is 8.0psi
F, when enoxaparin solution is concentrated into certain volume, in buffer container, add pure water, enoxaparin solution is entered and changes water desalination removal of impurities, while progressively regulating TMP to 13, Pf is 13.1psi, and Pp is-0.4psi, P r is 12.3psi, TMP is 13.0psi, and seepage velocity is 0.90ml/min, membrane flux 4.8L/m
2.h;
G, when changing water and reach 4.7 times, enoxaparin solution penetrating fluid is measured salt-free, disconnects buffer container, concentrated enoxaparin is to being difficult to have liquid to ooze, computer stops data gathering, save data, closes peristaltic pump, stops the experiment of enoxaparin ultrafiltration.Freeze-drying enoxaparin product obtains 78mg, and product meets GPC requirement in USP.
Example three
A, take enoxaparin 100g and be dissolved in 10L ultrapure water, be placed in port processing vessel, and connect buffer container, place liquid header on osmotic balance, osmotic balance makes zero;
B, pressure monitor and pump, by the external computer of USB interface data line, carry out parameter setting by software in computer, and selecting ultra-filtration membrane is 1kD, 1.25m
2;
The flow velocity 8L/min of c, setting pump, shearing force is 2716/s, closes through liquid port, disconnects port processing vessel and buffer container, opens pump, computer starts image data, is now the total reflux stage, moves after 5 minutes and opens through liquid port;
E, TMP is set is 8.0, and pump extracts enoxaparin solution from port processing vessel, and small portion infiltrates in liquid header, and in most of backflow entry port processing vessel, enoxaparin solution enters enriching stage,
F, when enoxaparin solution is concentrated into 4L, in buffer container, add pure water, enoxaparin solution is entered and changes water desalination removal of impurities, control molecular weight distribution, while progressively regulating TMP to 13, Pf is 14.0psi, and Pp is-0.4psi, Pr is 12.0psi, and TMP is 13.0psi, membrane flux 4L/m
2.h;
G, when changing water and reach 6 times, enoxaparin solution penetrating fluid is measured salt-free, disconnects buffer container, concentrated enoxaparin is to being difficult to have liquid to ooze, computer stops data gathering, save data, closes pump, stops the experiment of enoxaparin ultrafiltration.Freeze-drying enoxaparin product, meets GPC requirement in USP.
The method of the use ultrafiltration purification enoxaparin that the present invention discloses, the application in the removal of impurities of enoxaparin desalination and concentration, makes to filter hold-up volume little, product yield is high, and a step realizes removal of impurities desalination and concentration, fast, efficient gentle, shorten operating time and operability, reduce costs; By data logging, realize directly, from research and development scale, be amplified to production capacity easily.
The foregoing is only embodiments of the invention; not thereby limit the scope of the claims of the present invention; every equivalent structure or conversion of equivalent flow process that utilizes description of the present invention to do; or be directly or indirectly used in other relevant technical field, be all in like manner included in scope of patent protection of the present invention.
Claims (7)
1. a method of using tangential flow filtration technology purifying enoxaparin, is characterized in that, comprises the following steps:
A, pre-preparation: enoxaparin sample dissolution, in pure water, is then filled to after constant volume and in port processing vessel, forms enoxaparin solution, and connect buffer container, place liquid header on osmotic balance, osmotic balance makes zero;
B, parameter setting: pressure monitor and pump, by the external computer of USB interface data line, carry out parameter setting by software in computer;
C, the flow velocity of pump is set: close through liquid port, disconnect port processing vessel and buffer container, open pump, by pump, from porthandler, extract enoxaparin solution, pipeline by film upper liquid outlet enters hollow fiber film assembly, pressure transmitter is by data feedback to pressure monitor, and the pipeline that enoxaparin solution enters film fluid port last time refluxes, in automatic back pressure valve backflow entry port processing vessel;
D, enriching stage: use computer to start image data, move and open through liquid port after 5 minutes, pump extracts enoxaparin solution from port processing vessel, pipeline by film upper liquid outlet enters hollow fiber film assembly, pressure transmitter by data feedback to pressure monitor, the small portion liquid of enoxaparin solution infiltrates in liquid header by the pipeline of infiltration mouth, most of liquid of enoxaparin solution flows in inbound port processing vessel by the back of pipeline of film fluid port last time, progressively improve TMP, the flow velocity that TMP changes the interior penetrating fluid of pipeline of infiltration mouth is set, enoxaparin solution enters enriching stage, low molecular impurity and salt are removed simultaneously,
E, remove low molecular impurity and salt: when enoxaparin solution is concentrated into after certain volume, in buffer container, add pure water, because tubing system is inner sealing state, while penetrating liquid in buffer container, port is processed internal tank and is formed vacuum, pure water in buffer container is sucked, enoxaparin solution enters constant volume and changes the liquid stage, realize removing of low molecular impurity and salt, by removing low-molecular polysaccharide, Molecular regulator amount distributes simultaneously, observe pressure and seepage discharge and change, regulation and control TMP changes seepage velocity;
F, complete ultrafiltration: by measuring salts contg in penetrating fluid, determine and change water multiple, when changing water and reach 4-8 times, enoxaparin solution completes ultrafiltration, disconnects buffer container, concentrated enoxaparin is to being difficult to have liquid to ooze, computer stops data gathering, and save data, closes pump, stop the experiment of enoxaparin ultrafiltration, cleaning equipment;
G, index detect: by the freeze-drying of enoxaparin heparin sample, take quality, and calculated yield, product index detects.
2. hyperfiltration process according to claim 1, it is characterized in that, described osmotic balance is clamped with hollow fiber film assembly and is connected by infiltration, described hollow fiber film assembly is connected with pressure monitor with automatic back pressure valve respectively, described port processing vessel is connected between automatic back pressure valve and pressure monitor, described buffer container is connected with port processing vessel, described computer and pressure monitor are external, described liquid header is placed on above osmotic balance, and described pressure monitor is arranged on pump.
3. hyperfiltration process according to claim 1, is characterized in that, the flow velocity 70-90ml/min of described pump controls shearing force 2500 ~ 3500/s.
4. hyperfiltration process according to claim 1, is characterized in that, described hollow fiber film assembly comprises hollow fiber membrane filter and ultra-filtration membrane, and described ultra-filtration membrane is arranged on hollow fiber membrane filter inside.
5. hyperfiltration process according to claim 4, is characterized in that, described ultra-filtration membrane is modified poly (ether sulfone) film, molecular weight cut-off 1kD.
6. hyperfiltration process according to claim 4, it is characterized in that, on described hollow fiber membrane filter, be provided with three interfaces, comprise infiltration mouth, film upper liquid outlet and film fluid port last time, the middle side part that described infiltration mouth is arranged on hollow fiber membrane filter with see through liquid port and be connected, described film fluid port last time and film upper liquid outlet are arranged on respectively top and the bottom of hollow fiber membrane filter.
7. hyperfiltration process according to claim 1, it is characterized in that, described pressure transmitter comprises through liquid (Pp) pressure transmitter, phegma (Pr) pressure transmitter and feed liquid (Pf) pressure transmitter, described Pp pressure transmitter and Pf pressure transmitter are arranged on respectively the position of film upper liquid outlet and film fluid port last time, and described Pr pressure transmitter is arranged on the position of infiltration mouth.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105985454A (en) * | 2015-02-06 | 2016-10-05 | 苏州英诺凯生物医药科技有限公司 | Method for purifying enoxaparin |
| CN106188300A (en) * | 2015-05-07 | 2016-12-07 | 温州市人民医院 | A kind of method for quickly purifying keeping bladder chalone C antibody-latex covalent coupling complex activity |
| CN107778382A (en) * | 2017-11-21 | 2018-03-09 | 河北常山生化药业股份有限公司 | It is a kind of effectively to reduce the method that ethanol remains in Enoxaparin Sodium |
| CN112673027A (en) * | 2019-04-26 | 2021-04-16 | 罗威制药股份有限公司 | Method for obtaining low molecular weight heparins by tangential flow filtration |
| WO2022062011A1 (en) * | 2020-09-24 | 2022-03-31 | 九芝堂股份有限公司 | Method for purifying low-molecular weight fucosylated glycosaminoglycan by means of tangential flow ultrafiltration |
| EP3943513A4 (en) * | 2019-04-26 | 2022-12-21 | Laboratorios Farmacéuticos Rovi, S.A. | Method for obtaining low-molecular-weight heparins by means of tangential flow filtration |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850865A (en) * | 2006-05-24 | 2006-10-25 | 杭州九源基因工程有限公司 | Production method for purifying enoxaparin sodium |
| CN102050888A (en) * | 2010-12-13 | 2011-05-11 | 河北常山生化药业股份有限公司 | Method for preparing enoxaparin sodium |
| CN102731683A (en) * | 2012-07-17 | 2012-10-17 | 湖北亿诺瑞生物制药有限公司 | Method of separating natural low molecular heparin from heparin waste liquor |
| CN103232558A (en) * | 2013-05-02 | 2013-08-07 | 山东辰中生物制药有限公司 | Preparation method of high-quality low-molecular weight dalteparin sodium |
| CN103275246A (en) * | 2013-06-07 | 2013-09-04 | 山东辰中生物制药有限公司 | Production method of nadroparin calcium |
| CN203220855U (en) * | 2013-04-22 | 2013-10-02 | 杭州纽蓝科技有限公司 | Tangential flow ultrafiltration device |
| CN103342761A (en) * | 2013-07-15 | 2013-10-09 | 河北常山生化药业股份有限公司 | Technology for preparing enoxaparin sodium by membrane separation |
| CN103421128A (en) * | 2013-07-31 | 2013-12-04 | 山东辰中生物制药有限公司 | Method for preparing high-quality low molecular parnaparin sodium |
-
2014
- 2014-03-19 CN CN201410100250.2A patent/CN103936889A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850865A (en) * | 2006-05-24 | 2006-10-25 | 杭州九源基因工程有限公司 | Production method for purifying enoxaparin sodium |
| CN102050888A (en) * | 2010-12-13 | 2011-05-11 | 河北常山生化药业股份有限公司 | Method for preparing enoxaparin sodium |
| CN102731683A (en) * | 2012-07-17 | 2012-10-17 | 湖北亿诺瑞生物制药有限公司 | Method of separating natural low molecular heparin from heparin waste liquor |
| CN203220855U (en) * | 2013-04-22 | 2013-10-02 | 杭州纽蓝科技有限公司 | Tangential flow ultrafiltration device |
| CN103232558A (en) * | 2013-05-02 | 2013-08-07 | 山东辰中生物制药有限公司 | Preparation method of high-quality low-molecular weight dalteparin sodium |
| CN103275246A (en) * | 2013-06-07 | 2013-09-04 | 山东辰中生物制药有限公司 | Production method of nadroparin calcium |
| CN103342761A (en) * | 2013-07-15 | 2013-10-09 | 河北常山生化药业股份有限公司 | Technology for preparing enoxaparin sodium by membrane separation |
| CN103421128A (en) * | 2013-07-31 | 2013-12-04 | 山东辰中生物制药有限公司 | Method for preparing high-quality low molecular parnaparin sodium |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105985454A (en) * | 2015-02-06 | 2016-10-05 | 苏州英诺凯生物医药科技有限公司 | Method for purifying enoxaparin |
| CN106188300A (en) * | 2015-05-07 | 2016-12-07 | 温州市人民医院 | A kind of method for quickly purifying keeping bladder chalone C antibody-latex covalent coupling complex activity |
| CN107778382A (en) * | 2017-11-21 | 2018-03-09 | 河北常山生化药业股份有限公司 | It is a kind of effectively to reduce the method that ethanol remains in Enoxaparin Sodium |
| CN112673027A (en) * | 2019-04-26 | 2021-04-16 | 罗威制药股份有限公司 | Method for obtaining low molecular weight heparins by tangential flow filtration |
| EP3943513A4 (en) * | 2019-04-26 | 2022-12-21 | Laboratorios Farmacéuticos Rovi, S.A. | Method for obtaining low-molecular-weight heparins by means of tangential flow filtration |
| WO2022062011A1 (en) * | 2020-09-24 | 2022-03-31 | 九芝堂股份有限公司 | Method for purifying low-molecular weight fucosylated glycosaminoglycan by means of tangential flow ultrafiltration |
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