CN108089016A - A kind of lyophilized quality-control product of stabilization - Google Patents
A kind of lyophilized quality-control product of stabilization Download PDFInfo
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- CN108089016A CN108089016A CN201711247002.0A CN201711247002A CN108089016A CN 108089016 A CN108089016 A CN 108089016A CN 201711247002 A CN201711247002 A CN 201711247002A CN 108089016 A CN108089016 A CN 108089016A
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- 238000003908 quality control method Methods 0.000 title claims abstract description 83
- 230000006641 stabilisation Effects 0.000 title abstract description 5
- 238000011105 stabilization Methods 0.000 title abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 63
- 102000004190 Enzymes Human genes 0.000 claims abstract description 51
- 108090000790 Enzymes Proteins 0.000 claims abstract description 51
- 210000002966 serum Anatomy 0.000 claims abstract description 41
- 229930195725 Mannitol Natural products 0.000 claims abstract description 29
- 239000000594 mannitol Substances 0.000 claims abstract description 29
- 235000010355 mannitol Nutrition 0.000 claims abstract description 29
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract description 26
- 235000013922 glutamic acid Nutrition 0.000 claims abstract description 26
- 239000004220 glutamic acid Substances 0.000 claims abstract description 26
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 24
- 239000011159 matrix material Substances 0.000 claims abstract description 21
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 14
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims abstract description 8
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims abstract description 8
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims abstract description 8
- 239000004471 Glycine Substances 0.000 claims abstract description 7
- 108010088751 Albumins Proteins 0.000 claims abstract description 6
- 102000009027 Albumins Human genes 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 17
- 239000000843 powder Substances 0.000 claims description 16
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 claims description 11
- 108010082126 Alanine transaminase Proteins 0.000 claims description 11
- 108010003415 Aspartate Aminotransferases Proteins 0.000 claims description 11
- 102000004625 Aspartate Aminotransferases Human genes 0.000 claims description 11
- 238000004108 freeze drying Methods 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 229940009098 aspartate Drugs 0.000 claims 1
- 238000005057 refrigeration Methods 0.000 abstract description 6
- 238000012360 testing method Methods 0.000 description 21
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 6
- 238000007710 freezing Methods 0.000 description 6
- 230000008014 freezing Effects 0.000 description 6
- 238000011835 investigation Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000001133 acceleration Effects 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003223 protective agent Substances 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical class C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000011017 operating method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 108010050201 2-hydroxybutyrate dehydrogenase Proteins 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- VHJLVAABSRFDPM-IMJSIDKUSA-N L-1,4-dithiothreitol Chemical compound SC[C@H](O)[C@@H](O)CS VHJLVAABSRFDPM-IMJSIDKUSA-N 0.000 description 1
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical class [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 1
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004164 analytical calibration Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- -1 galactolipin Chemical compound 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical class [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003625 trehaloses Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/91188—Transferases (2.) transferring nitrogenous groups (2.6)
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
The application provides a kind of lyophilized quality-control product of stabilization.Specifically, a kind of quality-control product composition is provided, it includes following or be made up of：Serum matrix；At least one enzyme；Mannitol；Galactolipin；And glutamic acid, wherein not containing trehalose, not containing exogenous glycine, do not contain exogenous albumin.Lyophilized quality-control product provided in the disclosure has better accelerated stability, long-time stability, redissolves refrigeration/redissolution freeze-stable.
Description
Technical field
This application involves clinical examination fields.More particularly, to a kind of lyophilized or dry powder form quality-control product.
Background technology
In modern medicine system, the status of clinical examination becomes more and more important, particularly biochemical investigation.How into one
Step improves biochemical investigation quality, ensures the accuracy of biochemical investigation result, standardization, scientific, it has also become examine worker anxious
One of major subjects that need to be solved.
Quality management is to examine the core of discipline construction.In order to ensure the quality of biochemical investigation result, it is necessary to which biochemistry is examined
Test overall process controlled (Liu Fengchun et al., biochemical investigation quality control, China Health examine impurity, 2010, volume 20：906-
907)。
In biochemical investigation quality control, quality-control product plays key effect.According to the definition of IFCC, quality-control product (also make,
Quality Control object controls substance) refer to sample or solution dedicated for quality control purpose, it is impossible to be used in calibration.Quality-control product is divided into
Two kinds of definite value and underrange.
Quality control procedure is analyzed in clinical biochemical, and the periodic calibration and its quality control of Biochemical Analyzer are must can not
Few, it should all be carried out between new instrument installation, the reagent for replacing different batches, room or after Internal Quality Control appearance exception, each repair
The calibration of instrument.
Quality-control product is the quality control substance for in-vitro diagnosis, is a kind of be intended in the detecting system of medical usage
Substance, material, article or the equipment used, the purpose is to evaluate or confirmatory measurement precision, accuracy of measurement, due to reagent or
The performance characteristics such as the issuable analysis deviation of change detecting system of analytical instrument.
The reliability for the testing result that Biochemical Analyzer is combined with biochemical reagents depends on the monitoring of quality-control product, just can guarantee
Report the accuracy of result and the comparativity of different experiments room testing result.In Clinical laboratory test, it is often necessary to detect sample
Enzyme content/activity in this.However, being compared with small molecule determinand, enzyme is very easy to be denatured.It can be seen that quality-control product
Difference requires very high between stability, bottle.
More than one enzyme is generally comprised in quality-control product.Different enzymes has different chemical property, different activity.Cause
This, requirement of the different enzymes to environment is also different.However, in quality-control product, different types of enzyme is but in same environment, skill
Art personnel are difficult to take into account different enzymes to require the difference of stability.Thus, in the production process of quality-control product, it is intended to add in very
The protective ingredient of multiple types is to meet the needs of different enzymes.
CN102128917A discloses a kind of clinical biochemical quality control products and its preparation process, utilizes trehalose, Duo Zhongwen
Determine agent and the protectant combined effect of compound protein protective agent, complex enzyme, be prepared into multinomial clinical biochemical quality control products.In this application
In, protective agent (4.0 to 6.0g/L sodium chloride, 0.1 to 0.5g/L citric acids, 1.0 to 2.5g/L citric acids is included in quality-control product
Sodium, 0.5 to 1.5g/L sodium dihydrogen phosphates, 0.1 to 0.8g/L adenines, 0.5 to 2.0g/L compound protein protective agents HPD, 1.0 to
5.0g/L dithiothreitol (DTT)s, biological bacteriostatic agent)；Stabilizer (6.0 to 16.0g/L mannitol, 5.0 to 10g/L trehaloses, 2.0 to
5.0g/L glycerine, 1.0 to 5.0g/L compound enzymatic protective reagent HP, 2.5 to 6.0g/L compound enzyme stabilizers AES, 1.0 to 2.5g/L
BSA, 0.2 to 0.6g/g sodium azides).This method respectively protects the enzymes such as ALT, AST, TBIL or protein；Have at -20 DEG C
The effect phase is 12 months；It is 6 months that 2 to 8 DEG C, which preserve limited period,.However, added in quality-control product up to 15 kinds it is different types of
Protective ingredient, at least there are the inconvenience of following several respects for this：
1) production cycle is long, and the addition of each ingredient can need to increase corresponding operating procedure,
2) Quality Control Links are increased, each production stage is required for record, monitoring link；
3) uncertainty for chain of tracing to the source is brought；
4) increasing pollution may；
5) production ingredient greatly increases.
A kind of stable quality controlled serum α-hydroxybutyrate dehydrogenase and lactic acid dehydrogenase activity are disclosed in CN101893639A
Method, including to trehalose, mannitol, glycine, quality controlled serum and buffer solution mixing, freeze-drying the step of.
Method disclosed in CN101893639A makes the α-HBDH after freezing and LDH quality-control products preserve for a long time, and two after aquation redissolution
The activity of kind enzyme α-HBDH and LDH are without significant change.In this application, quality-control product includes 3% bovine serum albumin, 12% seaweed
Sugar, 5% mannitol, 200mM glycine, LDH, the phosphate buffer of 400U/L α-HBDH and 550U/L.
For the stability study of visiting reagent, this field predicts the failure period of product frequently with accelerated stability experiment
(for evaluating shelf stabilities, being sometimes referred to as long-time stability or the term of validity).Such method advantage is to study
Cycle is short (usual several weeks), without veritably by reagent storage 1 year, 2 years, even longer time.But acceleration for stabilization
The theoretical foundation of property is Arrhenius formula (Arrhenius equation).In order to ensure the accuracy of prediction, to suitable
With the formula, then there is more requirement to reagent.This is a kind of prediction ideally.However, the ingredient of biochemical reagents
Complexity, species are various, are not that any reagent can ideally be applicable in accelerated stability experiment to predict its real effect phase.
In addition, the stability of reagent should not narrowly be interpreted as shelf stabilities (long-time stability).This be because
It is, reagent in practical operation in use, being not merely to rest among the constant storehouse of environmental condition that (constant is warm and humid
Spend, avoid illumination direct projection, is shockproof), but may be exposed in the environment of variation.For example, it (is carried, top in transportational process
Winnow with a dustpan), the effect of mechanical force can be touched, the variation that can also run into temperature (although cold chain transportation may be employed, can not also avoid
Humiture timing constant).
For another example, in Clinical Institutions, the detection of sample is carried out on large scale equipment (Biochemical Analyzer).This behaviour
As mode multiple samples is allowed sequentially or simultaneously to be detected (from dozens of to a samples up to a hundred).So, reagent will be by steady from it
It spins off in fixed storage condition, and it is for use to open the upper machine of packaging.This process can not equally avoid the variation of humiture,
And ingress of air after sample is uncapped is faced with the factor of oxidation.Therefore, in this case, accelerated stability tests basic nothing
Method evaluates stability (iso standard 23640-2011, the In vitro diagnostic medical devices- of other aspects
Evaluation of stability of in vitro diagnostic reagents)。
For the quality-control product of dry powder form, before Clinical Institutions are for use, operating personnel is required for re-dissolve it.
However, the operation re-dissolved equally introduces destabilizing factor.
Therefore, technical staff needs to find a kind of new method so that does not add so multicomponent, still can but play same
Sample, even preferably stabilization.
The content of the invention
In view of the demand of this field, according to some embodiments of the disclosure, provides a kind of quality-control product composition,
It includes following or be made up of：
- serum matrix；
- at least one enzyme, the enzyme are selected from：Alanine aminotransferase, aspartate amino transferase or its group
It closes；
- mannitol；
- galactolipin；And
- glutamic acid.
In some embodiments, quality-control product composition does not contain exogenous trehalose.
In some embodiments, quality-control product composition does not contain exogenous glycine.
In some embodiments, quality-control product composition does not contain exogenous albumin.
In disclosure context, " exogenous " refers to, may be with micro- except in the raw materials such as serum matrix, mannitol, enzyme
Beyond the form of amount and existing or raw material carry in itself, trehalose, sweet ammonia are manually additionally introduced into quality-control product
Acid or albumin.
In some embodiments, the composition of the disclosure is dry powder or freeze-dried powder.
In some embodiments, in the composition of the disclosure, mannitol：Galactolipin：The mass ratio of glutamic acid is 5：3：
3。
In some embodiments, quality-control product composition redissolves as will be described, the concentration of the mannitol phase based on mass/volume
When in 5%.This counter can push away mannitol and be measured present in dry powder quality control products.
In some embodiments, if the quality-control product composition redissolved, the concentration of galactolipin is based on mass/volume
For 3%.
In some embodiments, if the quality-control product composition redissolved, the concentration of glutamic acid is based on mass/volume
For 3%.
In some embodiments, the serum matrix is derived from human serum.
In some embodiments, consider in bio-safety, the human serum is HBsAg is negative, HCV is negative, HIV is cloudy
Property and TP it is negative.
According to some embodiments, a kind of quality-control product composition is additionally provided, is made up of：
- human serum matrix, the human serum is HBsAg is negative, HCV is negative, HIV is negative, TP is negative；
- at least one enzyme, the enzyme are selected from：Alanine aminotransferase, aspartate amino transferase or its group
It closes；
- mannitol；
- galactolipin；And
- glutamic acid.
In some embodiments, the composition is dry powder or freeze-dried powder.In some embodiments, mannitol：Half
Lactose：The mass ratio of glutamic acid is 5：3：3.
In some embodiments, after the quality-control product composition redissolves, the concentration of mannitol is suitable based on mass/volume
The concentration for being equivalent to 3%, glutamic acid based on mass/volume in the concentration of 5%, galactolipin is equivalent to 3% based on mass/volume；
The concentration of alanine aminotransferase is equivalent to 400U/L, the concentration of aspartate amino transferase is equivalent to 400U/L.
According to some embodiments, purposes of the composition in enzyme quality-control product is prepared is additionally provided, wherein the composition
Comprising：Serum matrix, mannitol, galactolipin and glutamic acid.
In some embodiments, the composition does not contain exogenous trehalose, and the composition does not contain exogenous
Glycine, the composition do not contain exogenous albumin.
In some embodiments, mannitol：Galactolipin：The mass ratio of glutamic acid is 5：3：3.
In some embodiments, serum matrix is derived from human serum；The human serum is HBsAg is negative, HCV is negative, HIV
Negative, TP feminine genders.
In some embodiments, the enzyme quality-control product includes at least one enzyme, and the enzyme is selected from：Alanine amino turns
Move enzyme, aspartate amino transferase or its combination.
In some embodiments, the enzyme quality-control product is dry powder or freeze-dried powder.
According to some embodiments, a kind of method for improving enzyme quality-control product stability is additionally provided, including step：
1) at least one enzyme is provided, the enzyme is selected from：Alanine aminotransferase, aspartate amino transferase,
Or its combination；
2) composition is provided, the composition includes serum matrix, mannitol, galactolipin and glutamic acid, wherein sweet dew
Alcohol：Galactolipin：The mass ratio of glutamic acid is 5：3：3；
3) composition described at least one enzyme described in step 1) and step 2) is mixed；
The serum matrix is derived from human serum；The human serum is HBsAg is negative, HCV is negative, HIV is negative, TP is negative；
The order of step 1) and step 2) is interchangeable.
In some embodiments, the above method further includes the step of mixture is dried.
In some embodiments, drying is freeze-drying.
According to some embodiments, a kind of method for preparing enzyme quality-control product is additionally provided, including step：
1) at least one enzyme is provided, the enzyme is selected from：Alanine aminotransferase, aspartate amino transferase,
Or its combination；
2) composition is provided, the composition includes serum matrix, mannitol, galactolipin and glutamic acid, wherein sweet dew
Alcohol：Galactolipin：The mass ratio of glutamic acid is 5：3：3；
3) composition described at least one enzyme described in step 1) and step 2) is mixed,
4) operation is dried to the mixture obtained by step 3)；Preferably, the drying is freeze-drying；
The serum matrix is derived from human serum；The human serum is HBsAg is negative, HCV is negative, HIV is negative, TP is negative；
The order of step 1) and step 2) is interchangeable.
In some embodiments, it is freeze-dried according to following parameter：
It catches coolant-temperature gage and is arranged to -80 DEG C；Vacuum high alarm setting is arranged to 100Pa；The upper limit is arranged to 30Pa in vacuum range；
Vacuum range lower limit is arranged to 20Pa；Baffle temperature is arranged to -45 DEG C.
Specific embodiment
Embodiment
Embodiment 1：The composition of ALT quality-control products
It compares quality-control product and tests the composition of quality-control product referring to table 1.
The different compositions of table 1.ALT quality-control products
Embodiment 2：The composition of AST quality-control products
It compares quality-control product and tests the composition of quality-control product referring to table 2.
The different compositions of table 2.AST quality-control products
The preparation method of 3. quality-control product of embodiment
1) weighed according to the ingredient of Tables 1 and 2；
2) ingredient of weighing is added separately in serum matrix (or buffer solution), stirring and dissolving；
3) gained liquid quality control product are moved into dark glass container (such as brown ampoule)；
4) by the liquid quality control product after packing, put into freeze dryer sales kit (SK) and freezed.
Arrange parameter is as follows：
- catch -80 DEG C of coolant-temperature gage；- vacuum high alarm setting 100Pa；
Upper limit 30Pa in-vacuum range；- lower limit 20Pa；
- 45 DEG C of-baffle temperature,
Compressor, circulator and case low temperature valve are opened successively starts pre-freeze；
After baffle temperature is down to -40 DEG C (when about pre-freeze 3 is small), case low temperature valve is closed, opens cold-trap valve；
After cold-trap valve temperature drops to -50 DEG C, opening interval valve opens vacuum pump and starts to vacuumize；
Treat that vacuum degree drops to below 30Pa, into manually/curve temperature control, it is -10 DEG C to set baffle temperature, sets vacuum
It adjusts, when maintenance 16 to 20 is small；
Afterwards, baffle temperature is set to set vacuum uncomfortable to 25 DEG C, 6 it is small when after terminate it is lyophilized.
It is lyophilized to terminate, interval valve is closed, closes vacuum pump, cold-trap solenoid valve, compressor, circulating pump successively, is opened (preceding
Case) vent valve, takes out sample tamponade.
Test case
1. Biochemical Analyzer arrange parameter of test case
AST and ALT test kits use commercially available matured product, and to manufacturer source, there is no limit.Make kit
Each quality-control product prepared respectively in testing example 1 and 2.Automatic clinical chemistry analyzer used is Toshiba 40.
2. accelerated stability of test case (also making thermal stability)
37 DEG C of lyophilized quality-control products for being kept for 7 days will be put into and the lyophilized quality-control product of 2-8 DEG C of preservation dissolves simultaneously, examined simultaneously
It surveys, calculates (- 2-8 DEG C of concentration of 37 DEG C of concentration)/2-8 DEG C of concentration.
Table 3.ALT Acceleration study results
| 1 day | 3 days | 5 days | 7 days | |
| Control | 379.0 | 372.7 | 368.9 | 360.7 |
| Example 1 | 379.2 | 371.3 | 368.1 | 359.8 |
| Example 2 | 381.2 | 373.8 | 372.2 | 366.7 |
| Example 3 | 382.5 | 378.0 | 373.5 | 371.0 |
| Example 4 | 384.9 | 380.9 | 376.3 | 375.0 |
| Example 5 | 384.0 | 379.8 | 374.1 | 373.6 |
| Example 6 | 392.5 | 391.5 | 389.7 | 387.4 |
| Example 7 | 395.4 | 394.7 | 393.0 | 393.8 |
| Example 8 | 394.7 | 394.5 | 391.9 | 390.9 |
Table 4.AST Acceleration study experimental results
| 1 day | 3 days | 5 days | 7 days | |
| Control | 379.3 | 376.2 | 371.5 | 365.5 |
| Example 1 | 379.6 | 373.0 | 369.1 | 367.8 |
| Example 2 | 381.5 | 379.4 | 375.2 | 373.6 |
| Example 3 | 385.5 | 385.1 | 383.2 | 382.7 |
| Example 4 | 388.3 | 387.6 | 385.0 | 384.5 |
| Example 5 | 387.6 | 386.4 | 384.2 | 383.7 |
| Example 6 | 393.5 | 390.6 | 388.0 | 386.6 |
| Example 7 | 397.6 | 396.2 | 395.4 | 394.6 |
| Example 8 | 396.3 | 395.2 | 394.7 | 393.1 |
3. long-time stability of test case
Quality-control product is preserved 18 months at 2-8 DEG C.Compared with initial survey concentration (when being just made), calculate (18 months concentration-just
Examine concentration)/initial survey concentration.
Table 5.ALT long-time stability experimental results
| 6 months | 12 months | 18 months | |
| Control | 381.6 | 379.8 | 375.3 |
| Example 1 | 381.9 | 378.1 | 374.5 |
| Example 2 | 385.0 | 383.3 | 382.6 |
| Example 3 | 385.1 | 383.8 | 382.7 |
| Example 4 | 385.5 | 384.2 | 381.0 |
| Example 5 | 386.8 | 386.7 | 385.6 |
| Example 6 | 394.3 | 391.8 | 389.7 |
| Example 7 | 397.5 | 395.6 | 395.2 |
| Example 8 | 395.4 | 393.8 | 391.8 |
Table 6.AST long-time stability experimental results
| 6 months | 12 months | 18 months | |
| Control | 378.9 | 377.2 | 374.0 |
| Example 1 | 379.2 | 378.0 | 374.4 |
| Example 2 | 380.2 | 380.0 | 379.3 |
| Example 3 | 382.3 | 379.5 | 378.3 |
| Example 4 | 384.3 | 383.3 | 382.0 |
| Example 5 | 383.2 | 381.7 | 381.3 |
| Example 6 | 390.7 | 388.6 | 386.7 |
| Example 7 | 398.4 | 397.8 | 397.1 |
| Example 8 | 397.5 | 396.6 | 395.8 |
Test case 4. redissolves stability
1. redissolve refrigeration：
After quality-control product dissolving, detected after being refrigerated 3 days at 2-8 DEG C.Testing result calculates (cold compared with initial survey result
Hide 3 days concentration-initial survey concentration)/initial survey concentration.
Table 7.ALT redissolves refrigeration experimental result
Table 8.AST redissolves refrigeration experimental result
| 1 week | 2 weeks | 3 weeks | |
| Control | 389.1 | 386.3 | 382.5 |
| Example 1 | 389.4 | 385.3 | 381.4 |
| Example 2 | 390.8 | 389.7 | 385.8 |
| Example 3 | 392.2 | 390.4 | 388.7 |
| Example 4 | 394.6 | 393.7 | 390.0 |
| Example 5 | 392.9 | 389.2 | 388.1 |
| Example 6 | 396.0 | 394.6 | 392.6 |
| Example 7 | 398.9 | 398.6 | 396.7 |
| Example 8 | 397.6 | 397.6 | 395.5 |
2. redissolve freezing：
Quality-control product dissolving after, -20 DEG C refrigeration 15 days after detect, testing result with initial survey result compared with, calculate (freeze
15 days concentration-initial survey concentration)/initial survey concentration.
Table 9.ALT redissolves freezing experiment result
| 15 days | 30 days | 45 days | |
| Control | 389.2 | 387.6 | 384.2 |
| Example 1 | 389.2 | 385.7 | 380.8 |
| Example 2 | 391.7 | 388.0 | 385.0 |
| Example 3 | 392.9 | 391.5 | 387.7 |
| Example 4 | 395.3 | 392.8 | 389.7 |
| Example 5 | 395.4 | 391.6 | 388.5 |
| Example 6 | 399.4 | 396.9 | 394.9 |
| Example 7 | 400.7 | 400.4 | 398.4 |
| Example 8 | 400.5 | 399.0 | 396.9 |
Table 10.AST redissolves freezing experiment result
5. appearance of test case and dissolubility detection
The variation for being completely dissolved time used and course of dissolution is observed after adding in distilled water.
As a result：Each group is white or light yellow freeze-dried powder after lyophilized.Each group is light yellow settled solution after redissolving, nothing
Insoluble matter.
But ALT and AST control groups are completely dissolved needs 11 to 12 minutes.However, the test group of the application is 7 to 10
It is all completely dissolved within minute, the example 7 of especially ALT and AST were completely dissolved within 7 minutes to 8 minutes.This represents this Shen
Test composition please can provide better solubility property, and sample to be tested is more nearly on composition.
6. water content of test case
3 bottles of dried frozen aquatic products is randomly selected, measures the water content of dried frozen aquatic products.
Each group water content is can be controlled within 5% after lyophilized, meets the water content requirement of lyophilized quality-control product.Identical
Under lyophilized operating condition, for the example 6-8 of ALT and AST, water content can be even controlled within 3%.
According to the principle that pressure reduction boiling point declines, the moisture in material can directly distil from water without liquid phase as water
Vapour.Around this principle, first wet feed material can be freezed under freezing point, the moisture in raw material is made to become solid ice, Ran Hou
Under appropriate vacuum environment, ice is converted into steam and is removed, then with the water vapour coagulator in vacuum system by water vapour
Condensation, so that material obtains drying.
Specific theory is not limited to, for the example 6-8 of ALT and AST, composition provides more preferably freezing point, is conducive to
The distillation of moisture in lyophilized physical process.In other words, when being reduced to 5% water content, the quality-control product of the disclosure only needs
Shorter freeze-drying time can reach.
It is poor between 7. homogeneity of test case and bottle
1. homogeneity：1 bottle of replication 10 times measures average, standard deviation and CV by calculating.
It is 2. poor between bottle in batch：Measure 10 bottles of quality-control products each 1 time, it is poor between measure average, standard deviation and bottle to calculate.
As a result：Difference is can be controlled within 5% between each group homogeneity and bottle after lyophilized.However, the reality for ALT and AST
Example 1-8, difference is even can be controlled within 3% between homogeneity and bottle.It is not limited to specific theory, the component kind that control group is added
Class is more, this actually introduces more operational errors, thus affects the controllability of manufacturing process.However, clinically
For between quality-control product bottle-bottle, between batch-batch, it is desirable that more consistent better.Therefore, on the premise of stability is ensured, introducing is got over
Few component (and operating procedure) is better.
The combination quality-control product of test case 8.ALT and AST
In addition, the applicant also combines 400U/L ALT and 400U/L AST according to above-mentioned experiment.With reference to table 1
Composition carry out quality-control product preparation, differ only in addition to 400U/L ALT, also containing 400U/L AST.
Test result shows property indices and the result in test case 1-7 is suitable (data are not shown).This is confirmed
ALT and AST can be prepared into combination quality-control product, and the mutual portion of two kinds of enzymes influences respective stability and biology performance, can exist together
In same composition.
To sum up, in terms of accelerated stability, long-time stability, redissolution refrigeration/redissolution freeze-stable, carried in the disclosure
The lyophilized quality-control product supplied is significantly better than control quality-control product.It also, can when mannitol, galactolipin, glutamic acid are applied in combination
Better effect is provided.
Claims (9)
1. a kind of quality-control product composition, it includes following or be made up of：
- serum matrix；
- at least one enzyme, the enzyme are selected from：Alanine aminotransferase, aspartate amino transferase or its combination；
- mannitol；
- galactolipin；And
- glutamic acid,
Wherein, the composition does not contain exogenous trehalose, and the composition does not contain exogenous glycine, the composition
Exogenous albumin is not contained；
The composition is dry powder or freeze-dried powder；
Mannitol：Galactolipin：The mass ratio of glutamic acid is 5：3：3.
2. quality-control product composition according to claim 1, wherein：
After the composition redissolves, the concentration of mannitol is calculated as 5% by mass/volume；
After the composition redissolves, the concentration of galactolipin is calculated as 3% by mass/volume；And
After the composition redissolves, the concentration of glutamic acid is calculated as 3% by mass/volume.
3. quality-control product composition according to claim 1, wherein：
The serum matrix is derived from human serum；
The human serum is HBsAg is negative, HCV is negative, HIV is negative, TP is negative.
4. a kind of quality-control product composition, is made up of：
- human serum matrix, the human serum is HBsAg is negative, HCV is negative, HIV is negative, TP is negative；
- at least one enzyme, the enzyme are selected from：Alanine aminotransferase, aspartate amino transferase or its combination；
- mannitol；
- galactolipin；And
- glutamic acid,
Wherein, the composition is dry powder or freeze-dried powder；
Mannitol：Galactolipin：The mass ratio of glutamic acid is 5：3：3；
After the quality-control product composition redissolves, the concentration of mannitol be equivalent to based on mass/volume the concentration of 5%, galactolipin by
The concentration that mass/volume meter is equivalent to 3%, glutamic acid is equivalent to 3% based on mass/volume；Alanine aminotransferase it is dense
Degree is equivalent to 400U/L, the concentration of aspartate amino transferase is equivalent to 400U/L.
5. purposes of the composition in enzyme quality-control product is prepared, wherein the composition includes：
- serum matrix；
- mannitol；
- galactolipin；And
- glutamic acid,
Wherein, the composition does not contain exogenous trehalose, and the composition does not contain exogenous glycine, the composition
Exogenous albumin is not contained；
Mannitol：Galactolipin：The mass ratio of glutamic acid is 5：3：3；
The serum matrix is derived from human serum；The human serum is HBsAg is negative, HCV is negative, HIV is negative, TP is negative；
The enzyme quality-control product includes at least one enzyme, and the enzyme is selected from：Alanine aminotransferase, Aspartate amino turn
Move enzyme or its combination；And
The enzyme quality-control product is dry powder or freeze-dried powder.
6. a kind of method for improving enzyme quality-control product stability, including step：
1) at least one enzyme is provided, the enzyme is selected from：Alanine aminotransferase, aspartate amino transferase or its
Combination；
2) composition is provided, the composition includes serum matrix, mannitol, galactolipin and glutamic acid, wherein mannitol：Half
Lactose：The mass ratio of glutamic acid is 5：3：3；
3) composition described at least one enzyme described in step 1) and step 2) is mixed；
The serum matrix is derived from human serum；The human serum is HBsAg is negative, HCV is negative, HIV is negative, TP is negative；
The order of step 1) and step 2) is interchangeable.
7. according to the method described in claim 6, further include step：
Operation is dried to the mixture obtained by step 3)；
Preferably, the drying is freeze-drying.
8. a kind of method for preparing enzyme quality-control product, including step：
1) at least one enzyme is provided, the enzyme is selected from：Alanine aminotransferase, aspartate amino transferase or its
Combination；
2) composition is provided, the composition includes serum matrix, mannitol, galactolipin and glutamic acid, wherein mannitol：Half
Lactose：The mass ratio of glutamic acid is 5：3：3；
3) composition described at least one enzyme described in step 1) and step 2) is mixed,
4) operation is dried to the mixture obtained by step 3)；Preferably, the drying is freeze-drying；
The serum matrix is derived from human serum；The human serum is HBsAg is negative, HCV is negative, HIV is negative, TP is negative；
The order of step 1) and step 2) is interchangeable.
9. according to the method described in claim 8, wherein described freeze-drying proceeds as follows：
It catches coolant-temperature gage and is arranged to -80 DEG C；
Vacuum high alarm setting is arranged to 100Pa；
The upper limit is arranged to 30Pa in vacuum range；
Vacuum range lower limit is arranged to 20Pa；
Baffle temperature is arranged to -45 DEG C.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109100499A (en) * | 2018-06-21 | 2018-12-28 | 上海彧成生物科技有限公司 | A kind of formula of quality-control product freeze-drying liquid |
| CN109708946A (en) * | 2018-12-29 | 2019-05-03 | 宁波美康保生生物医学工程有限公司 | The preparation method of mixed linear high level for centrifugal type microfludic chip |
| CN109781991A (en) * | 2018-12-26 | 2019-05-21 | 深圳开立生物医疗科技股份有限公司 | A kind of c reactive protein saves liquid, calibration object, quality-control product and detection kit |
| CN110964783A (en) * | 2019-12-10 | 2020-04-07 | 郑州标源生物科技有限公司 | Quality control product of mitochondria aspartate aminotransferase and preparation method thereof |
| CN113109578A (en) * | 2020-04-30 | 2021-07-13 | 北京九强生物技术股份有限公司 | Biochemical quality control substance |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020146755A1 (en) * | 2001-01-31 | 2002-10-10 | Toshiyuki Baba | Quality control material |
| CN101105495A (en) * | 2007-07-31 | 2008-01-16 | 浙江省肿瘤医院 | Tumor mark quality control product preparation method |
| CN101893639A (en) * | 2010-02-11 | 2010-11-24 | 上海蓝怡科技有限公司 | Method for stabilizing activity of alpha-hydroxybutyricdehydrogenaseand lactic dehydrogenase of quality-control serum |
| CN103076213A (en) * | 2012-12-26 | 2013-05-01 | 宁波美康生物科技股份有限公司 | Preparation method of glycosylated albumin quality control |
| CN103399160A (en) * | 2013-08-07 | 2013-11-20 | 上海睿康生物科技有限公司 | Immunoturbidimetric assay apolipoprotein E detection kit |
-
2017
- 2017-12-01 CN CN201711247002.0A patent/CN108089016B/en active Active
- 2017-12-01 CN CN202310962584.XA patent/CN116990529A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020146755A1 (en) * | 2001-01-31 | 2002-10-10 | Toshiyuki Baba | Quality control material |
| CN101105495A (en) * | 2007-07-31 | 2008-01-16 | 浙江省肿瘤医院 | Tumor mark quality control product preparation method |
| CN101893639A (en) * | 2010-02-11 | 2010-11-24 | 上海蓝怡科技有限公司 | Method for stabilizing activity of alpha-hydroxybutyricdehydrogenaseand lactic dehydrogenase of quality-control serum |
| CN103076213A (en) * | 2012-12-26 | 2013-05-01 | 宁波美康生物科技股份有限公司 | Preparation method of glycosylated albumin quality control |
| CN103399160A (en) * | 2013-08-07 | 2013-11-20 | 上海睿康生物科技有限公司 | Immunoturbidimetric assay apolipoprotein E detection kit |
Non-Patent Citations (1)
| Title |
|---|
| 石建新等: "不同添加剂对自制同型半胱氨酸质控品质量的影响", 《检验医学与临床》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109100499A (en) * | 2018-06-21 | 2018-12-28 | 上海彧成生物科技有限公司 | A kind of formula of quality-control product freeze-drying liquid |
| CN109781991A (en) * | 2018-12-26 | 2019-05-21 | 深圳开立生物医疗科技股份有限公司 | A kind of c reactive protein saves liquid, calibration object, quality-control product and detection kit |
| CN109781991B (en) * | 2018-12-26 | 2022-06-24 | 深圳开立生物医疗科技股份有限公司 | C-reactive protein preserving fluid, calibrator, quality control product and detection kit |
| CN109708946A (en) * | 2018-12-29 | 2019-05-03 | 宁波美康保生生物医学工程有限公司 | The preparation method of mixed linear high level for centrifugal type microfludic chip |
| CN110964783A (en) * | 2019-12-10 | 2020-04-07 | 郑州标源生物科技有限公司 | Quality control product of mitochondria aspartate aminotransferase and preparation method thereof |
| CN110964783B (en) * | 2019-12-10 | 2023-08-29 | 郑州标源生物科技有限公司 | Quality control product of mitochondrial aspartic acid aminotransferase and preparation method thereof |
| CN113109578A (en) * | 2020-04-30 | 2021-07-13 | 北京九强生物技术股份有限公司 | Biochemical quality control substance |
| CN113109578B (en) * | 2020-04-30 | 2022-11-25 | 北京九强生物技术股份有限公司 | Biochemical quality control substance |
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