CN104181313B - Factor IX quality-control product preparation method - Google Patents
Factor IX quality-control product preparation method Download PDFInfo
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- CN104181313B CN104181313B CN201410449813.9A CN201410449813A CN104181313B CN 104181313 B CN104181313 B CN 104181313B CN 201410449813 A CN201410449813 A CN 201410449813A CN 104181313 B CN104181313 B CN 104181313B
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N2001/2893—Preparing calibration standards
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2496/00—Reference solutions for assays of biological material
- G01N2496/05—Reference solutions for assays of biological material containing blood cells or plasma
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Abstract
The present invention relates to the preparation method of clinical detection of blood coagulation preparation, concrete plasma thromboplastin component quality-control product preparation method, with anti-human coagulation factor IX monoclonal antibody immunity affinity column, many person-portions pooled plasma is carried out affinity chromatography, the plasma thromboplastin component removed in many person-portions pooled plasma is and lacks plasma thromboplastin component blood plasma; Again many person-portions pooled plasma is mixed according to a certain percentage with shortage plasma thromboplastin component blood plasma, be prepared into the plasma thromboplastin component quality-control product that plasma thromboplastin component content is variable concentrations level, add freeze drying protectant, packing, freeze drying, obtain plasma thromboplastin component quality-control product.Plasma thromboplastin component quality-control product prepared by the present invention, it is good that its product homogeneity, stability and dried frozen aquatic products melt rear stability again, imported product can be replaced to be used for the quality control of plasma thromboplastin component detection, to be conducive to reducing testing cost, to promote the ability that China is detected plasma thromboplastin component.
Description
Technical field
The present invention relates to the preparation method of clinical detection of blood coagulation preparation, concrete plasma thromboplastin component quality-control product preparation method.
Background technology
Plasma thromboplastin component measures has important clinical meaning.Along with coagulation Factor IX activity Interventions Requested are constantly extended to the every field in medical diagnosis on disease and treatment, use plasma thromboplastin component quality-control product to detect coagulation Factor IX activity and carry out Internal Quality Control and room interstitial and comment and just seem and be even more important.The reagent detected for plasma thromboplastin component at present, instrument are more, and different reagent and detecting instrument, Cleaning Principle are different, cause its result difference very large.No matter adopt which kind of method, carrying out Internal Quality Control and participating in that room interstitial comments is ensure that testing result has the necessary means of good reproducibility and comparability, and carrying out of these quality assurance measures all be unable to do without plasma thromboplastin component quality-control product.
The blood coagulation Quality Control thing that current clinical labororatory uses is generally multiparameter blood coagulation quality-control product, its exceptional value blood coagulation quality-control product other parameter except plasma thromboplastin component horizontal abnormality is also abnormal, be difficult to the accuracy ensureing pathologic sample plasma thromboplastin component measurement result, be also difficult to the validity ensureing that plasma thromboplastin component Internal Quality Control and room interstitial are commented simultaneously.
Domestic blood coagulation quality-control product is almost monopolized by external reagent manufacturer, valuable product and level is single, cannot meet the demand of the many activity levels of clinical examination, therefore, the plasma thromboplastin component quality-control product of multiple concentration levels of the domestic independent brand of development & production is extremely urgent.
Summary of the invention
For above-mentioned technical matters, the invention provides a kind of method and the acquisition plasma thromboplastin component quality-control product of preparing plasma thromboplastin component quality-control product.Plasma thromboplastin component quality-control product prepared by the inventive method is the multiple concentration level of plasma thromboplastin component, and other clotting factor content is in normal range; This product homogeneity and stability better, meet the clinical quality control requirement to the inspection of plasma thromboplastin component quality-control product.
In order to realize foregoing invention object, the invention provides following technical scheme: plasma thromboplastin component quality-control product preparation method, comprises the following steps:
(1) be add the blood of people's venous collection and anti-coagulants mix at 9: 1 with volume ratio, under 2 DEG C ~ 8 DEG C conditions centrifugal 15 minutes, relative centrifugal force(RCF) was 2500g, is separated and draws upper plasma, is mixed by many person-portions blood plasma, many person-portions pooled plasma; Anti-coagulants is citric acid three sodium solution, and its concentration is 0.109mol/L ~ 0.129mol/L.
(2) immune affinity chromatographic column balances under 10 DEG C ~ 18 DEG C conditions with damping fluid in advance, and damping fluid comprises 0.02mol/LTris, 0.15mol/LNaCl, 8mmol/LMgCl
2, pH7.25.
(3) many person-portions pooled plasma adds MgCl
2after, MgCl in many person-portions pooled plasma
2concentration is 4.5 ~ 5.5mmol/L.Upper immune affinity chromatographic column, collects the blood plasma flowed out below immune affinity chromatographic column, is and lacks plasma thromboplastin component blood plasma.
(4) will lack plasma thromboplastin component blood plasma and many person-portions pooled plasma as requested ratio mix, the plasma thromboplastin component quality-control product of variable concentrations level can be prepared into.
(5) the plasma thromboplastin component quality-control product of preparation is added freeze drying protectant, packing, freeze drying.The freeze drying protectant added, comprises 0.5 ~ 1.5%Hepes, 1 ~ 5% glycocoll, 0.5 ~ 5% sweet mellow wine that mass ratio accounts for plasma thromboplastin component quality-control product.
Plasma thromboplastin component quality-control product preparation method provided by the invention, with anti-human coagulation factor IX monoclonal antibody immunity affinity column, many person-portions pooled plasma is carried out affinity chromatography, the plasma thromboplastin component removed in many person-portions pooled plasma is and lacks plasma thromboplastin component blood plasma; Again many person-portions pooled plasma is mixed according to a certain percentage with shortage plasma thromboplastin component blood plasma, be prepared into the plasma thromboplastin component quality-control product that plasma thromboplastin component content is variable concentrations level, add freeze drying protectant, packing, freeze drying, obtain plasma thromboplastin component quality-control product.
In preparation method provided by the invention, the preparation method of anti-human coagulation factor IX monoclonal antibody immunity affinity column can the monoclonal antibody of connection plasma thromboplastin component of high degree of specificity be coupled on the Sepharose4B Ago-Gel of CNBr activation by a kind of, composition immune affinity chromatographic column.At Mg
2+under existent condition, when blood plasma is by this immune affinity chromatographic column, plasma thromboplastin component is adsorbed only, and the activity of other clotting factor does not become substantially.
Plasma thromboplastin component quality-control product prepared by the present invention, it is good that its product homogeneity, stability and dried frozen aquatic products melt rear stability again, imported product can be replaced to be used for the quality control of plasma thromboplastin component detection, to be conducive to reducing testing cost, to promote the ability that China is detected plasma thromboplastin component.
Embodiment
In conjunction with the embodiments, the present invention is set forth further:
Embodiment is to prepare the plasma thromboplastin component quality-control product that activity is 30%.
(1) be add the blood of people's venous collection and anti-coagulants mix at 9: 1 with volume ratio, under 2 DEG C ~ 8 DEG C conditions centrifugal 15 minutes, relative centrifugal force(RCF) was 2500g, is separated and draws upper plasma, is mixed by many person-portions blood plasma, many person-portions pooled plasma; Anti-coagulants is citric acid three sodium solution, and its concentration is 0.109mol/L ~ 0.129mol/L.
(2) immune affinity chromatographic column balances under 10 DEG C ~ 18 DEG C conditions with damping fluid in advance, and damping fluid comprises 0.02mol/LTris, 0.15mol/LNaCl, 8mmol/LMgCl
2, pH7.25.
(3) many person-portions pooled plasma adds MgCl
2after, MgCl in many person-portions pooled plasma
2concentration is 4.5 ~ 5.5mmol/L.Upper immune affinity chromatographic column, collects the blood plasma flowed out below immune affinity chromatographic column, is and lacks plasma thromboplastin component blood plasma.
(4) will lack plasma thromboplastin component blood plasma and many person-portions pooled plasma as requested ratio mix, prepare the plasma thromboplastin component quality-control product that coagulation Factor IX activity is about 30% concentration level.
(5) the plasma thromboplastin component quality-control product of preparation is added freeze drying protectant.Protective agent comprises 1%Hepes, 2% glycocoll, 2% sweet mellow wine.Carry out packing, freeze drying.
Test of product performance is tested:
(1) Product Activity detects
Detect reagent with SysmexCA-1500 Automatic coagulometer and supporting plasma thromboplastin component to detect embodiment plasma thromboplastin component quality-control product activity.
The coagulation factor activity chart of table 1 plasma thromboplastin component quality-control product
| Test item | II | V | VII | X | VIII | IX | XI | XII |
| Factor active (%) | 99.8 | 92.6 | 98.3 | 96.5 | 93.4 | 1.2 | 100.5 | 93.2 |
As seen from the above table, this preparation method products obtained therefrom specificity is good, can specific removal plasma thromboplastin component and on other clotting factor content substantially without impact.
(2) product homogeneity measures
In plasma thromboplastin component quality-control product prepared by embodiment, randomly draw 10 respectively, redissolve reconstruction accurately.
Detect reagent with SysmexCA-1500 Automatic coagulometer and supporting plasma thromboplastin component to detect embodiment plasma thromboplastin component quality-control product activity, result is as follows successively: percent activity (%) 29.9,30.2,30.0,29.8,29.0,29.5,30.3,30.1,30.2,29.7, mean value 29.9.
Plasma thromboplastin component quality-control product 3 bottles prepared by Example, redissolve reconstruction accurately, active 10 times of continuous detecting FIX after mixing, result is as follows: percent activity (%) 29.4,30.5,29.9,29.8,30.0,30.5,30.6,30.1,30.3,29.9; Mean value 30.1.
As calculated, be 0.39% between repeated CV value CV bottle between embodiment plasma thromboplastin component quality-control product bottle, illustrate that this horizontal plasma thromboplastin component quality-control product reaches the General Requirement (between batch interior bottle CV≤5.0%) of clinical testing for quality-control product homogeneity.
(3) product dried frozen aquatic products Detection of Stability
Plasma thromboplastin component quality-control product embodiment prepared and SIEMENSP quality-control product are placed in 37 DEG C of preservations, respectively at sampling in 1 day, 3 days, 5 days, 7 days, redissolve reconstruction accurately simultaneously.
Detect reagent with SysmexCA-1500 Automatic coagulometer and supporting plasma thromboplastin component to detect embodiment plasma thromboplastin component quality-control product activity, result is as follows:
Table 2 dried frozen aquatic products 37 DEG C of stability
Embodiment plasma thromboplastin component quality-control product 37 DEG C is placed 7 days, Activity Fluctuation range L EssT.LTssT.LT 5% before and after placing, suitable with the abnormal Quality Control blood plasma of commercially available import SIEMENS, can think that blood coagulation factor VIII quality-control product 37 DEG C placement prepared by the present invention is stable in 7 days.
(4) product redissolution Detection of Stability
Plasma thromboplastin component quality-control product embodiment prepared and SIEMENSP quality-control product redissolve reconstruction accurately, and be divided into two parts and be placed in 2 DEG C-8 DEG C respectively and room temperature (20 DEG C-25 DEG C) is preserved, coagulation Factor IX activity detection is carried out in sampling at regular intervals.
Detect reagent with SysmexCA-1500 Automatic coagulometer and supporting plasma thromboplastin component to detect embodiment plasma thromboplastin component quality-control product activity, result is as follows:
Table 3 redissolves stability
Under embodiment plasma thromboplastin component quality-control product redissolves and is placed on 2 DEG C ~ 8 DEG C and room temperature condition, 24 hours with 0 hour FIX:C without significant change, and the equal < 5% of Activity Fluctuation scope, suitable with the abnormal Quality Control blood plasma of commercially available import SIEMENS.Can think that this product redissolves rear 2 DEG C ~ 8 DEG C and room temperature and deposits and can keep stable in 24 hours.As can be seen here, the plasma thromboplastin component that prepared by the present invention has good uncork stability.
The above is only for a concentration level; it is the preferred embodiment of the present invention; what the present invention protected is whole technical process and product; should be understood that; for those skilled in the art; under the premise without departing from the principles of the invention, can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (4)
1. plasma thromboplastin component quality-control product preparation method, is characterized in that: comprise the following steps:
(1) be add the blood of people's venous collection and anti-coagulants mix at 9: 1 with volume ratio, centrifugal under 2 DEG C ~ 8 DEG C conditions, be separated and draw upper plasma, the upper plasma mixing after many person-portions are separated, many person-portions pooled plasma;
(2) immune affinity chromatographic column balances under 10 DEG C ~ 18 DEG C conditions with damping fluid in advance;
(3) many person-portions pooled plasma adds MgCl
2after, MgCl in many person-portions pooled plasma
2concentration is 4.5 ~ 5.5mmol/L, upper immune affinity chromatographic column, collects the blood plasma flowed out below immune affinity chromatographic column, is and lacks plasma thromboplastin component blood plasma;
(4) will lack plasma thromboplastin component blood plasma and many person-portions pooled plasma as requested ratio mix, be namely prepared into the plasma thromboplastin component quality-control product of variable concentrations level;
(5) the plasma thromboplastin component quality-control product of preparation is added freeze drying protectant, packing, freeze drying.
2. plasma thromboplastin component quality-control product preparation method according to claim 1, is characterized in that: described anti-coagulants is citric acid three sodium solution, and concentration is 0.109mol/L ~ 0.129mol/L.
3. plasma thromboplastin component quality-control product preparation method according to claim 1, is characterized in that: described damping fluid comprises 0.02mol/LTris, 0.15mol/LNaCl, 8mmol/LMgCl
2, pH7.25.
4. plasma thromboplastin component quality-control product preparation method according to claim 1, is characterized in that: described freeze drying protectant comprises 0.5 ~ 1.5%Hepes, 1 ~ 5% glycocoll, 0.5 ~ 5% sweet mellow wine that mass ratio accounts for plasma thromboplastin component quality-control product.
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| CN201410449813.9A CN104181313B (en) | 2014-09-04 | 2014-09-04 | Factor IX quality-control product preparation method |
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|---|---|---|---|
| CN201410449813.9A CN104181313B (en) | 2014-09-04 | 2014-09-04 | Factor IX quality-control product preparation method |
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| CN104181313B true CN104181313B (en) | 2015-11-18 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105175486A (en) * | 2015-10-20 | 2015-12-23 | 上海洲跃生物科技有限公司 | Preparation method of high-purity human coagulation factor IX |
| CN105330736A (en) * | 2015-11-06 | 2016-02-17 | 上海洲跃生物科技有限公司 | Method for preparing human blood coagulation factors IX and VII subcutaneously from cold-glue-removed blood plasma |
| CN107467013A (en) * | 2017-09-20 | 2017-12-15 | 上海贞元诊断用品科技有限公司 | Preparation method of quality control product universal plasma matrix capable of being stored for long time |
| CN110257358B (en) * | 2019-06-10 | 2023-05-19 | 广东双林生物制药有限公司 | Production method of high-purity human coagulation factor IX preparation |
| CN110346582B (en) * | 2019-07-15 | 2022-10-25 | 三诺生物传感股份有限公司 | Blood coagulation composite quality control product and preparation method thereof |
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| JPS59136657A (en) * | 1983-01-26 | 1984-08-06 | Green Cross Corp:The | Reagent for measuring eighth factor of blood clotting |
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| US5994140A (en) * | 1989-07-20 | 1999-11-30 | Analytical Control Systems, Inc. | Stable coagulation controls |
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