CN102350230B - Large-aperture composite ultrafilter membrane capable of removing pyrogen and its preparation method and use - Google Patents
Large-aperture composite ultrafilter membrane capable of removing pyrogen and its preparation method and use Download PDFInfo
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- CN102350230B CN102350230B CN2011101925595A CN201110192559A CN102350230B CN 102350230 B CN102350230 B CN 102350230B CN 2011101925595 A CN2011101925595 A CN 2011101925595A CN 201110192559 A CN201110192559 A CN 201110192559A CN 102350230 B CN102350230 B CN 102350230B
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- 239000002510 pyrogen Substances 0.000 title claims abstract description 76
- 239000002131 composite material Substances 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000000463 material Substances 0.000 claims abstract description 81
- 239000007924 injection Substances 0.000 claims abstract description 29
- 238000002347 injection Methods 0.000 claims abstract description 29
- 229920002492 poly(sulfone) Polymers 0.000 claims abstract description 21
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- 239000000203 mixture Substances 0.000 claims abstract description 15
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- 238000000108 ultra-filtration Methods 0.000 claims description 40
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- Separation Using Semi-Permeable Membranes (AREA)
Abstract
The invention discloses a large-aperture composite ultrafilter membrane capable of removing pyrogen. The large-aperture composite ultrafilter membrane capable of removing pyrogen comprises a mixed membrane material. The mixed membrane material is a mixture of a strongly hydrophilic membrane material and a weakly hydrophilic membrane material. The strongly hydrophilic membrane material is one or more of polysulfones, polyethersulfones and sulfonated polysulfones. The weakly hydrophilic membrane material is polyvinylidene fluoride or polyacrylonitrile. The invention also discloses a preparation method and a use of the large-aperture composite ultrafilter membrane capable of removing pyrogen. An application characteristic of the large-aperture composite ultrafilter membrane capable of removing pyrogen comprises realizing an injection pyrogen removal rate above 95% and having no obvious influence on drug active ingredients.
Description
Technical field
The present invention relates to a kind of composite hyperfiltration membrane, particularly a kind of pyrogen of can effectively removing can retain again large aperture composite hyperfiltration membrane of active ingredient in injection and its preparation method and application.
Background technology
The security of injection in recent years receives much concern, and wherein pyrogen reaction is one of clinical modal bad reaction.Ultrafiltration is a kind of more satisfactory depyrogenation method, but the pyrogen removal is conflict with the reservation of active ingredient all the time in the injection ultra-filtration process, therefore how when effectively removing pyrogen and guaranteeing preparation security, fully retaining the validity that active ingredient ensures preparation, is the greatest problem that current ultrafiltration faces in the injection application process.
Pyrogen (Pyrogen) is called again endotoxin (Endotoxin) usually, is mainly the pyrogenicity material produced by Gram-negative bacteria.Document shows that endotoxic molecular weight is several thousand to several ten thousand not wait, but owing to containing hydrophily polysaccharide and hydrophobicity LCFA in structure, character is similar to ionic surfactant, have in water solution system and assemble the characteristic that forms micelle, the molecular weight of micelle can reach hundreds of thousands to millions of, but this micelle state is subject to the impact of milipore filter material and destroyed in ultra-filtration process.
The milipore filter used in injection at present, its membrane aperture scope is generally 0.3 ten thousand-60,000 dalton, and membrane material mainly is divided into two classes: a class is strongly hydrophilic material milipore filter, as polysulfones or polyether sulfone or SPSF etc.; Another kind of is slightly water-wet material milipore filter, as Kynoar or polyacrylonitrile etc.When adopting the milipore filter ultrafiltration in above membrane material, aperture, find, when membrane aperture is less than 30,000 dalton, the pyrogen removal effect is better, but all has greater loss for the larger molecular weight composition contained in injection (as dextran etc.) or complicated traditional Chinese medicine ingredients (as ginsenoside and notoginsenoside etc.); And when membrane aperture is greater than 30,000 dalton, micelle outer rim sugar chain and intermembranously have an extremely strong affinity while contacting with strongly hydrophilic membrane material milipore filter due to pyrogen, cause the pyrogen micelle to disperse on the film surface, make pyrogen or to hang down and to form molecular state by the ultrafiltration fenestra with unimolecule, the effect of depyrogenation is poor.
CN 200810156112.0 discloses a kind of method for removing pyrogen from injections, has wherein related to large pore size ultrafiltration membrane, but there is no open material and preparation method with setting forth large pore size ultrafiltration membrane.
ZL 94104420.3 discloses a kind of polyacrylonitrile-polysulphone blended super-filter membrane and preparation method thereof.It is 1 that the method is selected the blending ratio of polyacrylonitrile and polysulfones: 1-1: 10, and the concentration in casting solution, between 10-17%, adds certain additive, prepare and obtain, its polyacrylonitrile film or PS membrane are compared, and under same rejection, the water flux of blended ultrafiltration membrane greatly increases.00130071 discloses a kind of polyblend milipore filter and preparation method thereof, by chloromethyl polysulphone and Kynoar, formed, the ratio that chloromethyl polysulphone accounts in total mixture is 10%-60%, but all there is no to disclose its aperture, also is not disclosed in the application of removing pyrogen in injection.
Summary of the invention
Goal of the invention: the purpose of this invention is to provide a kind of large aperture composite hyperfiltration membrane of removing pyrogen, formed by strongly hydrophilic membrane material and slightly water-wet membrane material.
Another object of the present invention is to provide the large aperture Compound Ultrafiltration membrane preparation method of this removal pyrogen.
A further object of the invention is to provide the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen of this removal pyrogen.
Technical scheme: a kind of large aperture composite hyperfiltration membrane of removing pyrogen, it is comprised of the hybrid films material, the mixture that described hybrid films material is strongly hydrophilic membrane material and slightly water-wet membrane material, described strongly hydrophilic membrane material be in polysulfones, polyether sulfone and SPSF any one or a few, described slightly water-wet membrane material is Kynoar or polyacrylonitrile, in described hybrid films material, the weight ratio of strongly hydrophilic membrane material and slightly water-wet membrane material is 2-4.5: 1, and the membrane aperture of described milipore filter is 50,000-500,000 dalton.
The large aperture composite hyperfiltration membrane of above-mentioned removal pyrogen, in the hybrid films material, the mixture that described strongly hydrophilic membrane material is polysulfones and polyether sulfone, described slightly water-wet membrane material is Kynoar.
The large aperture composite hyperfiltration membrane of above-mentioned removal pyrogen, the component that the hybrid films material comprises following parts by weight: polysulfones 8-12 part, polyether sulfone 4-6 part, Kynoar 4-6 part.
The large aperture composite hyperfiltration membrane of above-mentioned removal pyrogen, the component that the hybrid films material comprises following parts by weight: polysulfones is that 10 parts, polyether sulfone are 5 parts, and Kynoar is 5 parts.
The large aperture composite hyperfiltration membrane of above-mentioned removal pyrogen, the membrane aperture of described milipore filter is 50,000-350,000 dalton.
The large aperture Compound Ultrafiltration membrane preparation method of above-mentioned removal pyrogen comprises the following steps:
(1) get strongly hydrophilic membrane material and the slightly water-wet membrane material of formula ratio, add pore-foaming agent, the weight ratio of hybrid films material and pore-foaming agent is 10-22: 3-5, is dissolved in solvent, is heated to 40-60 ℃, mixes, and obtains masking stoste;
(2) masking stoste step (1) obtained is standing more than 24 hours, fully slaking;
(3) by the masking stoste after step (2) slaking, pressurization is extruded, filter out impurities, and spinneret spray silk, in 10-60 ℃ of coagulating bath of film silk, to obtain membrane aperture be 50,000-500,000 daltonian hollow-fibre membranes to film forming; Or the masking stoste after step (2) slaking is coated on the fiber support body, knifing is made film, and to obtain membrane aperture be 50,000-500,000 daltonian sheet frame films.
The large aperture Compound Ultrafiltration membrane preparation method of above-mentioned removal pyrogen, described pore-foaming agent is cetomacrogol 1000.
The large aperture Compound Ultrafiltration membrane preparation method of above-mentioned removal pyrogen, described solvent is dimethyl sulfoxide (DMSO), the consumption of solvent is meltage, needs to guarantee the dissolving fully of hybrid films material and pore-foaming agent.
The large aperture composite hyperfiltration membrane of above-mentioned removal pyrogen, the application in removing the injection pyrogen.
Beneficial effect: the ratio of (1) milipore filter of the present invention is preferred in hybrid films material strongly hydrophilic membrane material and slightly water-wet membrane material, guaranteed the appropriate affinity of milipore filter and pyrogen micelle, make pyrogen association micelle state in liquid not be destroyed, easily by wide-aperture milipore filter, held back and remove.Adopt limulus reagent test quantitatively to detect and show, the pyrogen clearance of milipore filter of the present invention is more than 95%, and most drug active ingredient is had no significant effect.(2) in this removal injection that the present invention proposes, the large aperture composite hyperfiltration membrane of pyrogen, improved the deficiency that existing hyperfiltration technique is removed pyrogen in injection, i.e. also loss simultaneously of active ingredient when pyrogen is removed.The inventor is through a large amount of experimental results show that with the daltonian Compound Ultrafiltration membrane filtration in membrane aperture 50,000-500,000, can not only effectively remove pyrogen, also retain as far as possible more large molecule active ingredient and useful pharmaceutic adjuvant in injection, as Tween 80, dextran etc., and Effective Component of Chinese Medicine is as each constituents such as ginsenoside etc.
The specific embodiment
Form by the following examples, foregoing of the present invention is described in further detail again, but this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example, all technology realized based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1: the preparation that aperture is 50,000 daltonian polymer composite hyperfiltration membranes
Concrete steps are as follows:
(1) part taking polysulfones by weight is 4 parts, and SPSF is 4 parts, and polyacrylonitrile is 2 parts, 3 parts of cetomacrogol 1000s, and dimethyl sulfoxide (DMSO) is 50 parts, standby; In material pot, polysulfones, SPSF and polyacrylonitrile are dissolved in to the polymer solution that dimethyl sulfoxide (DMSO) is made mixing, add cetomacrogol 1000 in polymer solution, 40 ℃ of left and right, stir, obtain masking stoste;
(2) masking stoste step (1) obtained is standing more than 24 hours, fully slaking;
(3) by the masking stoste after step (2) slaking, pressurization is extruded, filter out impurities, spinneret spray silk, the film silk is film forming in 10 ℃ of coagulating baths, making aperture is that (code name is 50,000 daltonian polymer mixed hollow-fibre membranes: A-1), or, on coating and fiber support body, knifing is made film, making aperture is that (code name is 50,000 daltonian polymer mixed sheet frame films: A-2), pure water cleans, and removes impurity.
Embodiment 2: the preparation that aperture is 100,000 daltonian polymer composite hyperfiltration membranes
Concrete steps are as follows:
(1) part taking polyether sulfone by weight is 12 parts, and Kynoar is 5 parts, 4 parts of cetomacrogol 1000s, and dimethyl sulfoxide (DMSO) is 75 parts, standby; In material pot, polyether sulfone and Kynoar are dissolved in to the polymer solution that dimethyl sulfoxide (DMSO) is made mixing, add cetomacrogol 1000 in polymer solution, 50 ℃ of left and right, stir, obtain masking stoste;
(2) masking stoste step (1) obtained is standing more than 24 hours, fully slaking;
(3) by the masking stoste after step (2) slaking, pressurization is extruded, filter out impurities, and spinneret spray silk, film forming in 20 ℃ of coagulating baths of film silk, making aperture is that (code name is 150,000 daltonian polymer mixed hollow-fibre membranes: B-1); Or, on coating and fiber support body, knifing is made film, making aperture is that (code name is: B-2), pure water cleans 150,000 daltonian polymer mixed sheet frame films, removes impurity.
Embodiment 3: the film-forming method that aperture is 200,000 daltonian polymer composite hyperfiltration membranes
Concrete steps are as follows:
(1) part taking polysulfones by weight is 10 parts, and polyether sulfone is 5 parts, and Kynoar is 5 parts, 4 parts of cetomacrogol 1000s, and dimethyl sulfoxide (DMSO) is 79 parts, standby; In material pot, polysulfones, polyether sulfone and Kynoar are dissolved in to the polymer solution that dimethyl sulfoxide (DMSO) is made mixing, add cetomacrogol 1000 in polymer solution, 60 ℃ of left and right, stir, obtain masking stoste;
(2) masking stoste step (1) obtained is standing more than 24 hours, fully slaking;
(3) by the masking stoste after step (2) slaking, pressurization is extruded, filter out impurities, and spinneret spray silk, film forming in 30 ℃ of coagulating baths of film silk, making aperture is that (code name is 200,000 daltonian polymer mixed hollow-fibre membranes: C-1); Or, on coating and fiber support body, knifing is made film, making aperture is that (code name is 200,000 daltonian polymer mixed sheet frame films: C-2); Pure water cleans, and removes impurity.
Embodiment 4: the film-forming method that aperture is 350,000 daltonian polymer composite hyperfiltration membranes
Concrete steps are as follows:
(1) part taking polysulfones by weight is 10 parts, and polyether sulfone is 6 parts, and Kynoar is 6 parts, 5 parts of cetomacrogol 1000s, and dimethyl sulfoxide (DMSO) is 85 parts, standby; In material pot, polysulfones, polyether sulfone and Kynoar are dissolved in to the polymer solution that dimethyl sulfoxide (DMSO) is made mixing, add cetomacrogol 1000 in polymer solution, 50 ℃ of left and right, stir, obtain masking stoste;
(2) masking stoste step (1) obtained is standing more than 24 hours, fully slaking;
(3) by the masking stoste after step (2) slaking, pressurization is extruded, filter out impurities, and spinneret spray silk, film forming in 40 ℃ of coagulating baths of film silk, making aperture is that (code name is 350,000 daltonian polymer mixed hollow-fibre membranes: D-1); Or, on coating and fiber support body, knifing is made film, making aperture is that (code name is 350,000 daltonian polymer mixed sheet frame films: D-2); Pure water cleans, and removes impurity.
Embodiment 5: the preparation that aperture is 500,000 daltonian polymer composite hyperfiltration membranes
Concrete steps are as follows:
(1) part taking SPSF by weight is 10 parts, and polyether sulfone is 4 parts, and polyacrylonitrile is 5 parts, 5 parts of cetomacrogol 1000s, and dimethyl sulfoxide (DMSO) is 78 parts, standby; In material pot, SPSF, polyether sulfone and polyacrylonitrile are dissolved in to the polymer solution that dimethyl sulfoxide (DMSO) is made mixing, add cetomacrogol 1000 in polymer solution, 50 ℃ of left and right, stir, obtain masking stoste;
(2) masking stoste step (1) obtained is standing more than 24 hours, fully slaking;
(3) by the masking stoste after step (2) slaking, pressurization is extruded, filter out impurities, and spinneret spray silk, film forming in 60 ℃ of coagulating baths of film silk, making aperture is that (code name is 500,000 daltonian polymer mixed hollow-fibre membranes: E-1); Or, on coating and fiber support body, knifing is made film, making aperture is that (code name is 500,000 daltonian polymer mixed sheet frame films: E-2); Pure water cleans, and removes impurity.
The impact of the different milipore filters of embodiment 6 on depyrogenation in XUESAITONG ZHUSHEYE and active ingredient
Experiment material:
(1) milipore filter: press the preparation method of embodiment 1-5, make composite hyperfiltration membrane, selecting respectively wherein code name is A-1, B-2, C-1, D-2, the milipore filter of E-1.All the other milipore filter materials, membrane aperture, source and form membrane see the following form:
Table 1 milipore filter commonly used and source
(2) instrument: Millipore ultrafilter; Agilent 1100 high performance liquid chromatographs; BET-16M bacteria endotoxin detector (Tianda Tianfa Technology Co., Ltd.).
(3) reagent: XUESAITONG ZHUSHEYE: get extract of panax notoginseng saponins (lot number: 040402, Yunnan Yuxi is natural drug Co., Ltd incomparably), add water and be mixed with the XUESAITONG ZHUSHEYE that concentration is 50mg/mL; Reference substance: Panax Notoginseng saponin R
1(lot number: 110745-200312), the ginsenoside Rg
1(lot number: 110703-200424), ginsenoside Rb
1(lot number: 110704-200318) all purchased from Nat'l Pharmaceutical & Biological Products Control Institute, the ginsenoside Rd (lot number: 070319, upper Hiroad standing grain medical sci-tech Development Co., Ltd); The dynamic turbidimetric TAL (lot number: 0711010, Zhanjiang Bo Kang marine organisms Co., Ltd).
Experimentation:
Get respectively XUESAITONG ZHUSHEYE, select above unlike material and aperture milipore filter to carry out ultrafiltration research, liquid after liquid and ultrafiltration before the sampling ultrafiltration.Detect before ultrafiltration in liquid after pyrogen content (E) and ultrafiltration pyrogen content in liquid (E ') with dynamic turbidimetric, calculate the clearance of pyrogen: clearance %=(E-E ')/E*100%; Measure before ultrafiltration in liquid after active constituent content (C) and ultrafiltration active constituent content in liquid (C ') with the HPLC method, calculate the active ingredient retention rate: retention rate %=C '/C*100%; The results are shown in Table 2.
The impact of the different milipore filters of table 2 on depyrogenation in XUESAITONG ZHUSHEYE and active ingredient
Result shows, as aperture, below 30,000 dalton, no matter is strongly hydrophilic material or the milipore filter of slightly water-wet material, and its efficiency of removing pyrogen is all higher, all over 95%.But seeing through of notoginseng triterpenes all had a significant effect, the notoginsenoside R of strongly hydrophilic material film, ginsenoside Rg1's transmitance higher (being 90-95%) wherein, and ginsenoside Rd, ginsenoside Rb1's transmitance very low (30-60%), the composition loss is serious; The impact of slightly water-wet material film is larger, and notoginsenoside R, ginsenoside Rg1's transmitance is about 50-80%, and ginsenoside Rd, the large section of ginsenoside Rb1 can not transmitances and lose, and actual seeing through is low to moderate 20-40%.
When aperture increases to 50,000 dalton, pyrogen is removed efficiency and is obviously reduced, and is about 80-90%.The notoginsenoside R of strongly hydrophilic material film, ginsenoside Rg1's transmitance are higher, be 95-96%, and ginsenoside Rd, ginsenoside Rb1's transmitance are increased to more than 50%, and composition still loses larger; It is poorer that the composition of slightly water-wet material film sees through, and notoginsenoside R, ginsenoside Rg1's transmitance is about 80-85%, and the seeing through still lower than 50% of ginsenoside Rd, ginsenoside Rb1.
When aperture reaches 100,000 dalton, can only remove the pyrogen lower than 70%.Strongly hydrophilic material film notoginsenoside R, ginsenoside Rg1's transmitance is more than 97%, and ginsenoside Rd, ginsenoside Rb1 also have good transmitance, all over 90%; No matter slightly water-wet material film is notoginsenoside R, ginsenoside Rg1, or ginsenoside Rd, ginsenoside Rb1, sees through lower than 92%.
Therefore, if conventional ultrafiltration film aperture is less than 30,000 dalton, remove pyrogen satisfactory for result, but the loss of the part composition of notoginseng triterpenes is very large; And aperture is while being amplified to 50,000 dalton, obviously reduced the former efficiency of reducing phlegm and internal heat, but the composition of notoginseng triterpenes still has partial loss, when aperture further is amplified to 100,000 dalton, although strongly hydrophilic material film can see through saponin preferably, but it is very low that pyrogen is removed efficiency, the safety guarantee specification requirement that does not reach injection.Therefore at present also do not have can adapt on domestic and international market and contain pseudo-ginseng or the constituent of ginseng injection former milipore filter that can reduce phlegm and internal heat again.
The composite hyperfiltration membrane that we adopt strongly hydrophilic material and slightly water-wet material composite material to make minute, on removal pyrogen and reservation compound components of panax notoginseng, windfall effect has appearred, when aperture increases to 100,000 dalton and when above, the composition transmitance is good, and the pyrogen clearance is more than 95%.
Embodiment 7: the impact of different milipore filters on depyrogenation in danshen injections and active ingredient
Experiment material:
(1) milipore filter: with embodiment 5.
(2) instrument: with embodiment 5.
(3) reagent: danshen injections: Shanghai Worldbest & Anhui Jinhui Pharmaceutical Co., Ltd.; Reference substance: Sodium Danshensu (lot number: 0855-200102), protocatechualdehyde (lot number: 110810-200205), tanshin polyphenolic acid B (lot number: 111562-200807) all purchased from Nat'l Pharmaceutical & Biological Products Control Institute; The dynamic turbidimetric TAL (lot number: 0711010, Zhanjiang Bo Kang marine organisms Co., Ltd).
Experimentation:
Get respectively danshen injections, select above unlike material and aperture milipore filter to carry out ultrafiltration research, liquid after liquid and ultrafiltration before the sampling ultrafiltration.Detect before ultrafiltration in liquid after pyrogen content (E) and ultrafiltration pyrogen content in liquid (E ') with dynamic turbidimetric, calculate the clearance of pyrogen: clearance %=(E-E ')/E*100%; Measure before ultrafiltration in liquid after active constituent content (C) and ultrafiltration active constituent content in liquid (C ') with the HPLC method, calculate the active ingredient retention rate: retention rate %=C '/C*100%; The results are shown in Table 3.
The impact of the different milipore filters of table 3 on depyrogenation in danshen injections and active ingredient
Experimental result shows, as aperture, below 30,000 dalton, its efficiency of removing pyrogen is all over 95%, and the transmitance of the danshensu in the red sage root and protocatechualdehyde is good, but tanshin polyphenolic acid B through all lower than 80%, certain influence is arranged.When aperture increases to 50,000 dalton, pyrogen is removed efficiency and is obviously reduced, and is about 80-90%, and seeing through of tanshin polyphenolic acid B is all also high to more than 90%.When aperture reaches 100,000 dalton, although on Components in Salvia miltiorrhiza without impact, the pyrogen clearance is down to below 70%.As the red sage roo drip liquid pyrogen content requires lower than 1EU/ml, during ultrafiltration, pyrogen removal efficiency must only have aperture to reach requirement at the following milipore filter of 30,000 dalton more than 98% in the market, but the loss of active ingredient tanshin polyphenolic acid B is larger.
The composite hyperfiltration membrane that adopts strongly hydrophilic material and slightly water-wet material composite material to make minute, on removal pyrogen and reservation effective component in red sage, windfall effect has appearred, when aperture increases to 50,000 dalton and when above, the composition transmitance is good, and the pyrogen clearance is more than 98%.
Embodiment 8: the impact of different milipore filters on depyrogenation and active ingredient in the Dextran 40 parenteral solution
Experiment material:
(1) milipore filter: with embodiment 5.
(2) instrument: with embodiment 5.
(3) reagent: Dextran 40 parenteral solution: get Dextran 40 raw material (molecular weight: 40000, the Chinese is far away becomes to create Science and Technology Ltd.) and add water, add water and be mixed with the Dextran 40 parenteral solution that concentration is 100mg/mL; Reference substance: Dextran 40 (lot number: 4102105) purchased from Shanghai Long March rich people medicine company Tongling Co., Ltd; The dynamic turbidimetric TAL (lot number: 0711010, Zhanjiang Bo Kang marine organisms Co., Ltd).
Experimentation:
Get respectively the Dextran 40 parenteral solution, select above unlike material and aperture milipore filter to carry out ultrafiltration research, liquid after liquid and ultrafiltration before the sampling ultrafiltration.Detect before ultrafiltration in liquid after pyrogen content (E) and ultrafiltration pyrogen content in liquid (E ') with dynamic turbidimetric, calculate the clearance of pyrogen: clearance %=(E-E ')/E*100%; Measure before ultrafiltration in liquid after active constituent content (C) and ultrafiltration active constituent content in liquid (C ') with the HPLC method, calculate the active ingredient retention rate: retention rate %=C '/C*100%; The results are shown in Table 3.
The impact of the different milipore filters of table 4 on depyrogenation in Dextran 40 and active ingredient
Result: dextran is the water-soluble polysaccharide medicine, molecular weight reaches 40,000 dalton, experiment shows, as the milipore filter aperture below 350,000, and during general greatly to 10 of membrane aperture ten thousand dalton, pyrogen is removed efficiency all lower than 60%, in the market still not for the former milipore filter of reducing phlegm and internal heat of dextran injection.The composite hyperfiltration membrane that employing strongly hydrophilic material of the present invention and slightly water-wet material composite material are made minute, when 35-50 ten thousand dalton of aperture, remove pyrogen and retain on macromolecule dextran and windfall effect occurred, the large molecule of energy selective removal reunion state pyrogen, the pyrogen clearance is more than 90%, and water-soluble macromolecule composition transmitance is good.
Claims (8)
1. the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen, it is characterized in that the large aperture composite hyperfiltration membrane, it is comprised of the hybrid films material, the mixture that described hybrid films material is strongly hydrophilic membrane material and slightly water-wet membrane material, described strongly hydrophilic membrane material is polysulfones, in polyether sulfone and SPSF any one or a few, described slightly water-wet membrane material is Kynoar or polyacrylonitrile, in described hybrid films material, the weight ratio of strongly hydrophilic membrane material and slightly water-wet membrane material is 2.4-4.5:1, the membrane aperture of described milipore filter is 50,000-500,000 dalton.
2. the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen according to claim 1, it is characterized in that the mixture that described in the composite hyperfiltration membrane hybrid films material of large aperture, the strongly hydrophilic membrane material is polysulfones and polyether sulfone, described slightly water-wet membrane material is Kynoar.
3. the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen according to claim 2, is characterized in that the component that the hybrid films material comprises following parts by weight: polysulfones 8-12 part, polyether sulfone 4-6 part, Kynoar 4-6 part.
4. the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen according to claim 3 is characterized in that the component that the hybrid films material comprises following parts by weight: polysulfones is that 10 parts, polyether sulfone are 5 parts, and Kynoar is 5 parts.
5. the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen according to claim 1, the membrane aperture that it is characterized in that described milipore filter is 50,000-350,000 dalton.
6. the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen according to claim 1 is characterized in that large aperture Compound Ultrafiltration membrane preparation method comprises the following steps:
(1) get strongly hydrophilic membrane material and the slightly water-wet membrane material of formula ratio, add pore-foaming agent, the weight ratio of hybrid films material and pore-foaming agent is 10-22:3-5, is dissolved in solvent, is heated to 40-60 ℃, mixes, and obtains masking stoste;
(2) masking stoste step (1) obtained is standing more than 24 hours, fully slaking;
(3) by the masking stoste after step (2) slaking, pressurization is extruded, filter out impurities, and spinneret spray silk, in 10-60 ℃ of coagulating bath of film silk, to obtain membrane aperture be 50,000-500,000 daltonian hollow-fibre membranes to film forming; Or the masking stoste after step (2) slaking is coated on the fiber support body, knifing is made film, and to obtain membrane aperture be 50,000-500,000 daltonian sheet frame films.
7. the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen according to claim 6, is characterized in that the pore-foaming agent described in the Compound Ultrafiltration membrane preparation method of large aperture is cetomacrogol 1000.
8. the application of large aperture composite hyperfiltration membrane in removing the injection pyrogen according to claim 6, is characterized in that the solvent described in the Compound Ultrafiltration membrane preparation method of large aperture is dimethyl sulfoxide (DMSO).
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| CN101683318A (en) * | 2008-09-28 | 2010-03-31 | 南京中医药大学 | Method for removing pyrogen from injections |
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| CN101683318A (en) * | 2008-09-28 | 2010-03-31 | 南京中医药大学 | Method for removing pyrogen from injections |
Non-Patent Citations (2)
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|---|
| PES/PVDF共混中空纤维膜的研制;齐文玉;《纺织科学研究》;20011231(第1期);第41-48页 * |
| 齐文玉.PES/PVDF共混中空纤维膜的研制.《纺织科学研究》.2001,(第1期), |
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