CN103308658B - Evaluation method for pyrogen removal process in traditional Chinese medicine injection - Google Patents
Evaluation method for pyrogen removal process in traditional Chinese medicine injection Download PDFInfo
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Abstract
The invention discloses an evaluation method for a pyrogen removal process in a traditional Chinese medicine injection, and relates to an evaluation method for a pyrogen removal process. The evaluation method aims at solving the problem of an existing traditional Chinese medicine injection that pyrogen removal method cannot be clearly evaluated or pyrogen removal effect is not scientific and rational. For materials in active carbon treatment and ultra-filtration treatment processes of concentrated liquid medicine of the traditional Chinese medicine injection, bacterial endotoxin is added to the liquid medicine, and bacterial endotoxin content determination is implemented before and after treatment, so as to make the pyrogen removal amount in the entire process clear and to evaluate the pyrogen removal effect of corresponding effect; when equipment is under an unloaded water-added operation state, the pyrogen removal capacity can achieve a log value not lower than 4, and when the equipment is under a loaded liquid medicine-added operation state, the pyrogen removal capacity can achieve a log value not lower than 3. The evaluation method can be used for evaluating the rationality and scientificity of the process, evaluating an industrial production line and providing an evaluation method of the application of ultra-filtration technology in the traditional Chinese medicine injection preparation field.
Description
Technical field
The present invention relates to the evaluation method that pyrogen removes technique.
Background technology
Pyrogen (Pyrogen), also known as endotoxin (Endotoxin), results from the mantle of Gram-negative (Gram-nagative) bacterium, that is the fragment of bacterium corpse.Its Main Ingredients and Appearance of further analysis is lipopolysaccharides (LPS) and lipoid A, is the active part of pyrogen.Their relative molecular mass is generally 10,000 ~ 2.5 ten thousand, and form association body in aqueous, relative molecular mass can reach 500,000 ~ 1,000,000.This kind of material has thermotolerance and chemical stability, is not easily eliminated.The injection injecting human body reaches 1 μ g/kg containing pyrogen amount and just can cause bad reaction, exothermic reaction occurs after 1 hour in injection usually, human body can be made to produce feel cold, shiver, generate heat, perspire, the symptom such as Nausea and vomiting, sometimes body temperature can rise to more than 40 DEG C, severe patient is even gone into a coma, collapse, as rescued not in time, can threat to life.This phenomenon is called " pyrogen reaction ".Therefore State Food and Drug Administration point out " safety of Chinese medicine injection revalues manufacture process evaluation engineering philosophy (trying) " " method and the condition of depyrogenation (or bacterial endotoxin) should be specified in production process; as activated charcoal consumption, disposal route, add opportunity, heating-up temperature and time etc., and investigate depyrogenation effect and the impact on pharmaceutical compositions.Correlative study data should be provided." therefore set up pyrogen in a kind of production process and remove degree evaluation method; the foundation of the method provides a kind of evaluation method, simultaneously also for hyperfiltration technique provides a kind of evaluation method in the application of traditional Chinese medicine formulation art to the rationality of the existing charcoal treatment of traditional Chinese medicine and ultrafiltration technology and science.
Current bacterial endotoxin method for quantitatively determining, the method for comparative maturity is turbidimetry and colourimetry two kinds, and colourimetry is highly sensitive, quantitative all high with precision, usually carries out in the scope of 0.006 ~ 15EU/mL quantitatively, but operation more complicated.Mainly be used in the endotoxin mensuration aspect in blood, body fluid at present.And turbidimetry is simple to operate, economical, highly sensitive, sensing range is wide.Usually carry out within the scope of 0.006 ~ 300EU/mL quantitatively, but need instrumentation, because this reaction can not stop, so error at measurment is large.
At present, at semi-quantitative method---the gel method that the controlling of production process of reality also all adopts pharmacopeia to provide with research, the method can not quantitatively can not be evaluated the depyrogenation effect in production technology.
Kinetic turbidimetric assay controls also just to be in conceptual phase at traditional Chinese medicine end product quality, kinetic turbidimetric assay then can carry out assay to bacterial endotoxin, the endotoxic content in sample can be read more accurately, can demarcate self-control bacterial endotoxin simultaneously, solve commodity bacterium Endotoxin spikes indicating value less (being generally less than 10000Eu) and the more expensive problem of price, adopt self-control bacterial endotoxin to make the endotoxin challenge research of industrial equipment become possibility.As: " bacterial endotoxin sizing technique Study On The Activated Carbon and ultrafiltration pyrogen remove technique " (medical Leader that Li Cunyu etc. announce, 02 phase in 2010: 142-144 page), method adopts lean solution research experiment, do not conform to the dense solution of joining in actual production, owing to using endotoxin indicator, be difficult to realize the challenge of endotoxin heavy dose, ultimate guarantee pyrogen the criterion thoroughly removed can be gone in regulation evaluation useless, assay only measures the liquid after activated charcoal and hyperfiltration treatment, the not pollution liquid before treatment of replicate determination simultaneously, polluting liquid just utilizes the sign value of indicator convert and draw, the comparability adopting distinct methods to obtain between two groups of data is relatively poor, its result also scientifically can not evaluate the effect removing pyrogen.
Summary of the invention
The object of the invention is to solve in existing traditional Chinese medicine technique, depyrogenation method can not clearly or depyrogenation effect can not the problem evaluated of scientific and reasonable carrying out, and provide pyrogen in a kind of traditional Chinese medicine and remove the evaluation method of technique.
In a kind of traditional Chinese medicine of the present invention, pyrogen removes the evaluation method of technique, carries out according to following steps:
One, in the dense vehicle of traditional Chinese medicine through charcoal treatment or hyperfiltration treatment, after adding bacterial endotoxin mixing, pyrogen is removed;
Two, the bacteria endotoxin content before adding step one and after removing pyrogen measures respectively, judges pyrogen removal effect, if evaluation index meets or exceeds evaluation of estimate, then think that evaluated technique depyrogenation is effective with evaluation index;
Wherein, described evaluation index is the logarithm value with the content decline multiple removed after pyrogen before bacterial endotoxin adds;
Described evaluation of estimate is: equipment is under zero load adds water running status, and the log value that pyrogen removes multiple is not less than 4, and equipment adds liquid running status in load, and the log value that pyrogen removes multiple is not less than 3.
The present invention comprises following beneficial effect:
Method provided by the invention be for traditional Chinese medicine ingredients after liquid, for the depyrogenation technique that traditional Chinese medicine is conventional, the application of charcoal absorption and hyperfiltration technique, adopt the test of bacterial endotoxin aggressiveness, the bacterial endotoxin of normal level of pollution up to ten thousand times is added beyond in liquid or water, after pyrogen removal system by existing technique, pyrogen effectively can be removed, bacteria endotoxin content measures and adopts kinetic turbidimetric assay, use bacteria endotoxin detector detects, the parallel comparison of sample Simultaneously test before and after process, shielding assay different time and batch error measured.Adopt self-control bacterial endotoxin to make the challenge of Large Copacity liquid test like this and become possibility, have the endotoxin amount of enough capacity.Evaluation result judges its validity with the logarithm value of final endotoxin amount decline multiple, American Pharmacopeia and European Pharmacopoeia respectively with decline 3 with 4 logarithms (3log and 4log) be effective, with reference to above-mentioned standard, the evaluation index of the program is: equipment to add water running status in zero load, pyrogen removal ability should reach log value and be not less than 4, apparatus of load adds liquid running status, and pyrogen removal ability should reach log value and be not less than 3.Realize the evaluation of the pyrogen removal effect in various process for preparation of injection, be applicable to the evaluation of the bacterial endotoxin challenge trial of existing technology ensuring system, the evaluation of the process conditions in new technology research process and the optimization of parameter and choice experiment, provides a kind of evaluation method of the science for oneself kind simultaneously to the propagation and employment of some new technologies (as hyperfiltration technique).This evaluation method is also applicable to the depyrogenation system appraisal of industrial production line simultaneously, the limit ability to ward off risks of challenge industrial production line, the applicability of the locating injection agent industry pyrogen security system of science.
Embodiment
Embodiment one: in a kind of traditional Chinese medicine of present embodiment, pyrogen removes the evaluation method of technique, carries out according to following steps:
One, in the dense vehicle of traditional Chinese medicine through charcoal treatment or hyperfiltration treatment, after adding bacterial endotoxin mixing, pyrogen is removed;
Two, the bacteria endotoxin content before adding step one and after removing pyrogen measures respectively, judges pyrogen removal effect, if evaluation index meets or exceeds evaluation of estimate, then think that evaluated technique depyrogenation is effective with evaluation index;
Wherein, described evaluation index is the logarithm value with the content decline multiple removed after pyrogen before bacterial endotoxin adds;
Described evaluation of estimate is: equipment is under zero load adds water running status, and the log value that pyrogen removes multiple is not less than 4, and equipment adds liquid running status in load, and the log value that pyrogen removes multiple is not less than 3.
The method that present embodiment provides be for traditional Chinese medicine ingredients after liquid, for the depyrogenation technique that traditional Chinese medicine is conventional, the application of charcoal absorption and hyperfiltration technique, adopt the test of bacterial endotoxin aggressiveness, the bacterial endotoxin of normal level of pollution up to ten thousand times is added beyond in liquid or water, after pyrogen removal system by existing technique, pyrogen effectively can be removed, bacteria endotoxin content measures and adopts kinetic turbidimetric assay, use bacteria endotoxin detector detects, the parallel comparison of sample Simultaneously test before and after process, shielding assay different time and batch error measured.Adopt self-control bacterial endotoxin to make the challenge of Large Copacity liquid test like this and become possibility, have the endotoxin amount of enough capacity.Evaluation result judges its validity with the logarithm value of final endotoxin amount decline multiple, American Pharmacopeia and European Pharmacopoeia respectively with decline 3 with 4 logarithms (3log and 4log) be effective, with reference to above-mentioned standard, the evaluation index of the program is: equipment to add water running status in zero load, pyrogen removal ability should reach log value and be not less than 4, apparatus of load adds liquid running status, and pyrogen removal ability should reach log value and be not less than 3.Realize the evaluation of the pyrogen removal effect in various process for preparation of injection, be applicable to the evaluation of the bacterial endotoxin challenge trial of existing technology ensuring system, the evaluation of the process conditions in new technology research process and the optimization of parameter and choice experiment, provides a kind of evaluation method of the science for oneself kind simultaneously to the propagation and employment of some new technologies (as hyperfiltration technique).This evaluation method is also applicable to the depyrogenation system appraisal of industrial production line simultaneously, the limit ability to ward off risks of challenge industrial production line, the applicability of the locating injection agent industry pyrogen security system of science.
Embodiment two: present embodiment and embodiment one unlike: the bacterial endotoxin unit described in step one is more than or equal to 30000Eu/mL.Other is identical with embodiment one.
Embodiment three: present embodiment and embodiment one or two unlike: described bacteria endotoxin content measures and adopts kinetic turbidimetric assay, use bacteria endotoxin detector detects, with the parallel comparison of bacterial endotoxin Simultaneously test of removing after pyrogen before bacterial endotoxin adds.Other is identical with embodiment one or two.
Embodiment four: one of present embodiment and embodiment one to three are carried out measuring unlike: described bacteria endotoxin content and referred to and carried out being diluted to the sample for detecting with 10 times of gradients by testing sample.Other is identical with one of embodiment one to three.
Embodiment five: one of present embodiment and embodiment one to four unlike: removal pyrogen described in step one adopts activated charcoal or hyperfiltration technique to carry out.Other is identical with one of embodiment one to four.
Embodiment six: one of present embodiment and embodiment one to five unlike: if evaluation index does not reach evaluation of estimate, then calculate the adsorption rate of bacterial endotoxin, specify science and rationality that activated charcoal applies at traditional Chinese medicine.Other is identical with one of embodiment one to five.
Embodiment seven: one of present embodiment and embodiment one to six are unlike described bacterial endotoxin adsorption rate=1-(test bit/comparison values) × 100%.Other is identical with one of embodiment one to six.
Embodiment eight: one of present embodiment and embodiment one to seven unlike: the addition adding bacterial endotoxin described in step one is 1000 times that are greater than detectability.Other is identical with one of embodiment one to seven.
Beneficial effect of the present invention is verified by following instance:
The concrete enforcement technical scheme of evaluation method of the present invention is as follows, evaluate by removing technique to the pyrogen of dual coptis powder, Danshen injection (freeze-drying) two kinds, these two kinds are powder-injection, depyrogenation technique workshop section is dense vehicle, the dilution ratio that endotoxin content detects is 100 times, therefore the relative and endotoxic challenge concentration of aqueous solution is also greater than 100 times, water, all adopt charcoal absorption and hyperfiltration technique for depyrogenation in these two kinds of injection techniques, tested by the pyrogen challenge of bench scale, confirm this evaluation of programme feasibility with this.
Example 1
1 activated charcoal depyrogenation effect assessment
1..1 the required instrument and equipment of test and reagent
Instrument: BET-72 bacteria endotoxin detector Tianjin Tianda Tianfa Science and Technology Co. Ltd.
ZH-2BLENDER eddy mixer Tianjin Pharmacopoeia Standard Instrument Factory
Peristaltic pump CL-25 type Beijing film device responsibility company limited of rising sun nation;
Reagent: needle-use activated carbon lot number: 090901(180 DEG C of activation 4h);
Supplier: Zhejiang activated charcoal branch office of Hang Mu Industrial Co., Ltd;
Quantitative detection tachypleus amebocyte lysate specification: 0.03eu lot number: 1002260;
Producer: Zhanjiang Bo Kang Marine Bio Co., Ltd.
Bacterial endotoxin working standard specification: 10eu/ props up lot number: 0911200;
Producer: Zhanjiang Andusi Biology Co., Ltd.
Haikang longevity Medical Devices Co., Ltd.'s manufacture (lot number: 080927) on disposable syringe 1mL
Syringe filter (aseptic apyrogeneity filter) JETBIOFIL
there is provided, LotNo.:081117-051;
The dense vehicle of swap buffers: workshop provides (de-charcoal before) lot number: 100320,100321,100322;
The dense vehicle of the red sage root: workshop provides (de-charcoal before) lot number: 100401,100402,100403;
Self-control pyrogen (E. coli broth process) specification > 50000eu/mL;
1..2 evaluation method
1.2.1 pyrogen filtration result test in deionized water
Remove ionized water 45mL, (method for making is: by E. coli broth 121 DEG C of pyroprocessing 30min to add 5mL self-control pyrogen, ultrasonic disruption 2h, with 0.45 μm of membrane filtration, namely obtains pyrogen) mixing after, get 1mL in contrast, all the other add 0.25g activated charcoal, are heated to micro-boiling, and keep 15min, filter, get 1mL filtered solution as need testing solution.
Contrast solution gradient dilution (10 times of gradients are diluted), gets 1/1000 and 1,/10,000 two concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Need testing solution liquid is got stoste (not diluting) and is diluted to 1/10 of original content; Get 0.1mL respectively, add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
1.2.2 depyrogenation effect test in dual coptis powder liquid
Get swap buffers liquid 40mL, after adding the mixing of 10mL self-control pyrogen, get 1mL in contrast, all the other add 0.25g activated charcoal, are heated to micro-boiling, and keep 15min, filter, get 1mL filtered solution as need testing solution.
Contrast solution gradient dilution (10 times of gradients are diluted), gets 1/100,1/1000 and 1,/10,000 3 concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Need testing solution gradient dilution (10 times of gradients are diluted), gets 1/100,1/1000 and 1,/10,000 3 concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Revision test 3 batches.
1.2.3 depyrogenation effect test in Danshen injection liquid
Get red sage root 40mL, after adding the mixing of 10mL self-control pyrogen, get 1mL in contrast, all the other add 0.25g activated charcoal, are heated to micro-boiling, and keep 15min, filter, get 1mL filtered solution as need testing solution.
Contrast solution gradient dilution (10 times of gradients are diluted), gets 1/100,1/1000 and 1,/10,000 3 concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Need testing solution gradient dilution (10 times of gradients are diluted), gets 1/100,1/1000 and 1,/10,000 3 concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Revision test 3 batches.
1.2.4 evaluation method: judge its validity with the logarithm value of final endotoxin amount decline multiple, American Pharmacopeia and European Pharmacopoeia respectively with decline 3 with 4 logarithms (3log and 4log) be effective, with reference to above-mentioned standard, the evaluation index of the program is: equipment to add water running status in zero load, the log value that pyrogen removes multiple is not less than 4, apparatus of load adds liquid running status, and the log value that pyrogen removes multiple is not less than 3.Then calculating Endotoxin adsorption rate as do not reached above-mentioned evaluation index, specifying science and rationality that activated charcoal applies at traditional Chinese medicine.
Endotoxin adsorption rate=1-(test bit/comparison values) * 100%
1..3 experimental result
Activated charcoal depyrogenation effect assessment test findings in table 1-1 water
Activated charcoal depyrogenation effect assessment test findings in table 1-2 injection liquid
Note: sample be each lot number and detect time different extension rate numbering.
1..4 evaluation conclusion
Activated charcoal can reach Log value 3.8 to the removal effect of bacterial endotoxin, meet the removal effect of American Pharmacopeia about bacterial endotoxin, but do not meet the relevant regulations of European Pharmacopoeia, illustrate that activated charcoal is really effective for removal pyrogen, but can not thoroughly remove when heavy dose of bacterial endotoxin pollutes.
Activated charcoal can effective pyrogen in the dense vehicle of Adsorption swap buffers and the dense vehicle of the red sage root, and wherein in swap buffers liquid, adsorption rate is greater than 70%, and in danshen solution adsorption rate more than 90%.Illustrate that powder-injection adds a large amount of pyrogen of charcoal absorption (bacterial endotoxin) in the fabrication process scientific and reasonable, but above result also shows, for the bacterial endotoxin of heavy dose, activated charcoal can not Adsorption completely.
Example 2
2 ultra filtration membrane depyrogenation effect assessments
Dual coptis powder and Danshen injection adopt Millipore company of the U.S. to produce cross-flow ultrafiltration system in producing, in tangential flow filtration (TFF), liquid tangentially flows through film surface, and part solution is pressed through filter membrane by the transmembrane pressure that fluid produces, part of damming then circulating filtration in systems in which.Can wash away film surface while filtration, make film surface keep clean, keep stable filter velocity.
2..1 test apparatus equipment and reagent
Instrument: BET-72 bacteria endotoxin detector Tianjin Tianda Tianfa Science and Technology Co. Ltd.
ZH-2BLENDER eddy mixer Tianjin Pharmacopoeia Standard Instrument Factory
Peristaltic pump CL-25 type Beijing film device responsibility company limited of rising sun nation;
Ultrafiltration post: 10k, 1ft
2, Regenerated.Cellulose (MilliporeCorporation.BillericaMA01821);
Reagent: quantitatively detect tachypleus amebocyte lysate specification: 0.03Eu lot number: 1002260;
Producer: Zhanjiang Bo Kang Marine Bio Co., Ltd.
Bacterial endotoxin working standard: specification: 10Eu/ props up, lot number: 0911200;
Producer: Zhanjiang Andusi Biology Co., Ltd.
Disposable syringe, 1mL, upper Haikang longevity Medical Devices Co., Ltd.'s manufacture (lot number: 080927)
The dense vehicle workshop of swap buffers provides lot number: 100501,100502,100503;
The dense vehicle workshop of the red sage root provides lot number: 100504,100505,100506;
Self-control pyrogen (E. coli broth process) specification > 50000Eu/mL;
2..2 evaluation method
2.2.1 pyrogen filtration result test in deionized water
Remove ionized water 1000mL, (method for making is: by E. coli broth 121 DEG C of pyroprocessing 30min, ultrasonic disruption 2h to add 50mL self-control pyrogen, with 0.45 μm of membrane filtration, namely obtain pyrogen), get 1mL in contrast, all the other ultrafiltration, get 1mL filtered solution as need testing solution.
Contrast solution gradient dilution (10 times of gradients are diluted), gets 1/1000 and 1,/10,000 two concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Need testing solution liquid is got stoste (not diluting) and is diluted to 1/10 of original content, gets 0.1mL respectively, adds 0.1mL tachypleus amebocyte lysate, Instrument measuring.
2.2.2 pyrogen filtration result test in swap buffers liquid
Get swap buffers liquid 500mL, add 100mL and make pyrogen by oneself, get 1mL in contrast, all the other ultrafiltration, get 1mL filtered solution as need testing solution.
Contrast solution gradient dilution, gets 1/1000 and 1,/10,000 two concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Need testing solution gradient dilution, gets 1/100 and 1/1,000 two concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Revision test 3 batches.
2.2.3 pyrogen filtration result test in danshen solution
Get danshen solution 500mL, add 100mL and make pyrogen by oneself, get 1mL in contrast, all the other ultrafiltration, get 1mL filtered solution as need testing solution.
Contrast solution gradient dilution, gets 1/1000 and 1,/10,000 two concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Need testing solution gradient dilution, gets 1/100 and 1/1,000 two concentration, gets 0.1mL respectively, all add 0.1mL tachypleus amebocyte lysate, Instrument measuring.
Revision test 3 batches.
2.2.4 evaluation method: judge its validity with the logarithm value of final endotoxin amount decline multiple, American Pharmacopeia and European Pharmacopoeia respectively with decline 3 with 4 logarithms (3log and 4log) be effective, with reference to above-mentioned standard, the evaluation index of the program is: equipment to add water running status in zero load, the log value that pyrogen removes multiple is not less than 4, apparatus of load adds liquid running status, and the log value that pyrogen removes multiple is not less than 3.Then calculating Endotoxin adsorption rate as do not reached above-mentioned evaluation index, specifying science and rationality that activated charcoal applies at traditional Chinese medicine.
Endotoxin adsorption rate=1-(test bit/comparison values) * 100%
2..3 evaluation result
Table 2-1: ultra filtration membrane depyrogenation effect assessment result
Note: control group data all adopt the minimum value of measurement result.Test results endotoxin does not all detect, because sensitivity of the limulus reagent is 0.03Eu/mL, deionized water is that stoste detects, then testing result is < 0.03, and swap buffers and the minimum extension rate of red sage root group are 100 times, so testing result is < 3.
2..4 evaluation conclusion
Test adopt the ultra filtration membrane of specification can completely filtering pyrogen.Adopt the bacterial endotoxin in ultra filtration membrane interception water can reach Log value and be greater than 4 by checking institute, the bacterial endotoxin removed in shuanghuanglian powder injection and the dense vehicle of Danshen injection all can reach Log value and be greater than 3, effectively can to ensure in final products that pyrogen remains and reach requirement.
Claims (2)
1. in traditional Chinese medicine, pyrogen removes an evaluation method for technique, it is characterized in that the evaluation method of pyrogen removal technique in described traditional Chinese medicine is carried out according to following steps:
One, in the dense vehicle of traditional Chinese medicine through charcoal treatment or hyperfiltration treatment, after adding bacterial endotoxin mixing, pyrogen is removed;
Two, the bacteria endotoxin content before adding step one and after removing pyrogen measures respectively, judges pyrogen removal effect, if evaluation index meets or exceeds evaluation of estimate, then think that evaluated technique depyrogenation is effective with evaluation index;
Wherein, described evaluation index is the logarithm value with the content decline multiple removed after pyrogen before bacterial endotoxin adds;
Described evaluation of estimate is: equipment is under zero load adds water running status, and the log value that pyrogen removes multiple is not less than 4, and equipment adds liquid running status in load, and the log value that pyrogen removes multiple is not less than 3; Described bacterial endotoxin unit is more than or equal to 30000Eu/mL; Described bacteria endotoxin content measures and adopts kinetic turbidimetric assay, uses bacteria endotoxin detector to detect, with the parallel comparison of bacterial endotoxin Simultaneously test of removing after pyrogen before bacterial endotoxin adds; Described bacteria endotoxin content carries out measuring the sample referring to and carry out testing sample to be diluted to 10 times of gradients confession detection; The addition adding bacterial endotoxin described in step one is 1000 times that are greater than detectability.
2. pyrogen removes the evaluation method of technique in a kind of traditional Chinese medicine according to claim 1, it is characterized in that the removal pyrogen described in step one adopts activated charcoal or hyperfiltration technique to carry out.
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Effective date of registration: 20211214 Address after: 150000 room a307-169, building 20, innovation and entrepreneurship Plaza, science and technology innovation city, high tech Industrial Development Zone, Harbin, Heilongjiang Province (178 Xiuyue Street) Patentee after: Harbin Pharmaceutical Group traditional Chinese Medicine Co.,Ltd. Address before: 150078 No. 243 Airport Road, Daoli District, Heilongjiang, Harbin Patentee before: The Second Chinese Medicine Factory, Harbin Pharmaceutical Group Co.,Ltd. |