CN116410258B - Factor XI deficiency plasma protective agent and application thereof - Google Patents
Factor XI deficiency plasma protective agent and application thereof Download PDFInfo
- Publication number
- CN116410258B CN116410258B CN202310392199.6A CN202310392199A CN116410258B CN 116410258 B CN116410258 B CN 116410258B CN 202310392199 A CN202310392199 A CN 202310392199A CN 116410258 B CN116410258 B CN 116410258B
- Authority
- CN
- China
- Prior art keywords
- factor
- plasma
- protective agent
- kit
- blood
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000003223 protective agent Substances 0.000 title claims abstract description 52
- 201000007219 factor XI deficiency Diseases 0.000 title abstract description 5
- 108010074864 Factor XI Proteins 0.000 claims abstract description 63
- 230000000694 effects Effects 0.000 claims abstract description 44
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims abstract description 36
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims abstract description 36
- 239000003114 blood coagulation factor Substances 0.000 claims abstract description 36
- 230000002950 deficient Effects 0.000 claims abstract description 36
- 238000001514 detection method Methods 0.000 claims abstract description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 12
- 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 description 11
- 239000004471 Glycine Substances 0.000 claims description 11
- 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 description 11
- 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 description 11
- 229940119744 dextran 40 Drugs 0.000 claims description 11
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 11
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 claims description 10
- 229920001993 poloxamer 188 Polymers 0.000 claims description 10
- 229940044519 poloxamer 188 Drugs 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims description 6
- 239000007995 HEPES buffer Substances 0.000 claims description 6
- 229960003405 ciprofloxacin Drugs 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 210000002381 plasma Anatomy 0.000 abstract description 103
- 238000000034 method Methods 0.000 abstract description 19
- 229940019700 blood coagulation factors Drugs 0.000 abstract description 18
- 238000004108 freeze drying Methods 0.000 abstract description 15
- 230000015271 coagulation Effects 0.000 abstract description 11
- 238000005345 coagulation Methods 0.000 abstract description 11
- 230000008569 process Effects 0.000 abstract description 11
- 239000004094 surface-active agent Substances 0.000 abstract description 8
- 229910017053 inorganic salt Inorganic materials 0.000 abstract description 7
- 239000003755 preservative agent Substances 0.000 abstract description 7
- 230000002335 preservative effect Effects 0.000 abstract description 7
- 239000007853 buffer solution Substances 0.000 abstract description 6
- 102000004169 proteins and genes Human genes 0.000 abstract description 5
- 108090000623 proteins and genes Proteins 0.000 abstract description 5
- 230000002779 inactivation Effects 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 2
- 238000005259 measurement Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 12
- 206010053567 Coagulopathies Diseases 0.000 description 9
- 230000035602 clotting Effects 0.000 description 8
- 239000011159 matrix material Substances 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000008859 change Effects 0.000 description 6
- 238000012417 linear regression Methods 0.000 description 6
- 102100030563 Coagulation factor XI Human genes 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 230000010100 anticoagulation Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 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 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 108010080865 Factor XII Proteins 0.000 description 2
- 102000000429 Factor XII Human genes 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 238000010219 correlation analysis Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229960004222 factor ix Drugs 0.000 description 2
- 229940012413 factor vii Drugs 0.000 description 2
- 229960000301 factor viii Drugs 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 238000012792 lyophilization process Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000008055 phosphate buffer solution Substances 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 238000012802 pre-warming Methods 0.000 description 2
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 102100037529 Coagulation factor V Human genes 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 102100029117 Coagulation factor X Human genes 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 208000033131 Congenital factor II deficiency Diseases 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 201000007176 Factor XII Deficiency Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 208000007646 Hypoprothrombinemias Diseases 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 201000000839 Vitamin K Deficiency Bleeding Diseases 0.000 description 1
- 206010047634 Vitamin K deficiency Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000009852 coagulant defect Effects 0.000 description 1
- 229940105756 coagulation factor x Drugs 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 208000011664 congenital factor XI deficiency Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 208000009429 hemophilia B Diseases 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000031915 positive regulation of coagulation Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 201000007183 prothrombin deficiency Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 208000016794 vitamin K deficiency hemorrhagic disease Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention relates to the technical field of in-vitro diagnostic reagents, in particular to a factor XI deficiency plasma protective agent and application thereof. The invention provides a protective agent comprising a buffer solution, a freeze-drying protective agent, a surfactant, a preservative and inorganic salt, factor XI deficient plasma comprising human factor XI plasma and the protective agent, and application of the factor XI deficient plasma in preparing a blood coagulation factor activity detection reagent or a kit. The protective agent provided by the invention can effectively ensure the stability and activity of the protein in human factor XI blood plasma, protect the protein in blood plasma from inactivation caused by the freeze-drying process, and further improve the product performance of the blood plasma containing human factor XI. The factor XI deficient plasma provided by the invention is suitable for most of the common full-automatic coagulation analyzers in the market.
Description
Technical Field
The invention relates to the technical field of in-vitro diagnostic reagents, in particular to a factor XI deficiency plasma protective agent and application thereof.
Background
The molecular mechanism of hemostasis is the process of sequential activation by a series of clotting factors, from the activation of coagulation to the formation of a plasma clot, which is dependent on both the extrinsic and intrinsic coagulation pathways (including the common pathway of coagulation).
Factor XI (F XI) is a serine protease zymogen, once known as plasma thromboplastin precursor (Plasma Thromboplastin Antecedent, PTA), a plasma coagulation factor involved in contact in the intrinsic coagulation pathway. Factor XI is essential for maintaining the endogenous pathway and plays a key role in the amplification of the coagulation cascade. During the clotting process, a deficiency in factor XI (either due to genetic factors or due to acquired factors) will affect the balance of the entire clotting system. Congenital defects in coagulation factor XI are associated with typical hemophilia a and other hemorrhagic diseases such as christmas disease, PTA deficiency, hageman-trait and hypoprothrombinemia, etc. Acquired coagulation disorders may involve the deficiency of multiple coagulation factors. They are often associated with trauma, liver disease, vitamin K deficiency or anticoagulant therapy. For the monitoring of these diseases, accurate diagnosis of the activity of coagulation factor XI and other coagulation factors and other factors responsible for the disease is required.
For the detection of the blood coagulation factor XI, two main products are mainly used in the market at present, one is mainly used for detecting the protein content of the blood coagulation factor, and the other is mainly used for detecting the activity of the blood coagulation factor, namely a clotting method, and the principle is based on the correction capability of detecting the clotting time (APTT) extension of the blood plasma of the blood deficiency factor caused by the to-be-detected sample. The coagulation method has the advantages of simple operation, accurate result, capability of truly reflecting the activity of the coagulation factors which actually play a role in the coagulation process, and the like, and is widely applied.
During plasma clotting, the absence of any clotting factor will affect the overall clotting response, and thus the status of the clotting factor will directly affect the stability of factor XI deficient plasma. In order to ensure the stability of factor XI lacking plasma, the factor XI is usually prepared into a freeze-dried product or frozen plasma is stored in an ultralow temperature environment, but the activity of the blood coagulation factors is extremely easy to be reduced in the processes of freeze-drying, storing and the like, so that the activity of each blood coagulation factor in the plasma is ensured to be a precondition for the stability of the plasma.
In recent years, due to the strong popularization and use of the full-automatic coagulation analyzer, the factor XI activity measurement is automated, so that the operation threshold of the factor XI measurement is reduced, and the accuracy of the detection result is greatly improved. Thus, the demand for reagents related to factor XI assays is increasing. At present, a plurality of manufacturers produce kits for measuring the factor XI, but the kits are foreign products, have high price and long purchase period, are easily influenced by factors such as external environment and the like in the transportation and storage process, and lead to the inactivation of the blood coagulation factors, so that the stability of the kits is reduced.
Disclosure of Invention
In view of the above, the technical problem to be solved by the present invention is to provide a factor XI-deficient plasma protective agent and application thereof, which can effectively protect the activity of factor XI-deficient plasma before and after lyophilization, and has the advantages of simple preparation method, low cost and strong stability.
The invention provides a protective agent, which comprises buffer solution, freeze-drying protective agent, surfactant, preservative and inorganic salt, wherein,
The buffer solution comprises at least one of HEPES buffer solution, tris buffer solution and phosphate buffer solution;
the protective agent comprises at least one of sucrose, mannitol, sorbitol, glycine, dextran-40 and trehalose;
The surfactant comprises at least one of poloxamer 188 and sodium cholate;
The preservative comprises at least one of NaN 3, merthiolate and ciprofloxacin;
The inorganic salt includes at least one of sodium chloride and potassium chloride.
Compared with the selection of other components, the components in the protective agent provided by the invention are matched with each other, so that a more stable freeze-drying system is provided for preparing freeze-dried blood plasma, the activities of blood coagulation factors and fibrinogen in the blood plasma can be protected to the greatest extent, the blood plasma is effectively stabilized, and a more accurate technical effect is obtained.
In some embodiments, the buffer is HEPES buffer, the protectant is glycine, dextran-40, and trehalose, the surfactant is poloxamer 188, the preservative is ciprofloxacin, and the inorganic salt is sodium chloride. Compared with other reagents, the components are tightly matched with each other, so that the compatibility is strong, the preparation of freeze-dried blood plasma can be more effectively matched, and meanwhile, the activities and the stability of each coagulation factor and fibrinogen in the blood plasma are taken into consideration, so that more accurate technical effects are obtained.
Preferably, the protective agent consists of water, 123.6-357.5 g/L HEPES buffer solution, 10-50 g/L trehalose, 10-100 g/L glycine, 10-50 g/L dextran-40, 1-5 g/L poloxamer 188, 1-5 g/L ciprofloxacin and 0.1-1 g/L sodium chloride, and the pH value of the protective agent is 7.8.
A comparison experiment is carried out on the freeze-dried plasma prepared by the components and the protective agent with the concentration range and a commercial product, and repeated detection is carried out on the normal range fixed value plasma and the pathological range fixed value plasma, so that the result shows that the variation Coefficient (CV) of the normal range fixed value plasma and the pathological range fixed value plasma measured by the plasma provided by the invention is smaller than that of the commercial product, the repeatability is better, and a more accurate technical effect is obtained.
Further preferably, the protective agent consists of water, 240g/L HEPES buffer solution, 20g/L trehalose, 50g/L glycine, 20g/L dextran-40, 2g/L poloxamer 188, 2.5g/L ciprofloxacin and 0.2g/L sodium chloride, and the pH value of the protective agent is 7.8.
Experiments show that at the concentration, the freeze-dried plasma prepared by the protectant has the best effect and the best experimental repeatability.
The invention also provides application of the protective agent in preparing blood coagulation factor deficient plasma or a kit containing the blood coagulation factor deficient plasma.
Preferably, the clotting factor deficient plasma comprises factor XI deficient plasma.
Further preferably, the factor XI deficient plasma is human blood plasma lacking XI, in particular human negative blood plasma, from which blood coagulation factor XI is removed to a level of less than or equal to 1%.
The invention provides factor XI deficient plasma or a kit comprising factor XI deficient plasma, including human factor XI deficient plasma and said protective agent.
Preferably, the volume ratio of the protective agent to the human factor XI-deficient plasma is (1-3): 7-9.
Further preferred, the volume ratio of the protective agent to the human factor XI-deficient plasma is 2:8.
The invention also provides application of the factor XI deficient plasma in preparing a blood coagulation factor activity detection reagent or a kit.
The invention provides a method for detecting factor XI activity in human blood plasma by using a blood coagulation factor activity detection kit, which comprises the following specific steps:
① . Diluting the plasma sample with a diluent in a ratio of 1:5 (returning to room temperature of 15-25 ℃), sucking the plasma sample into a test tube by a pipette, pre-warming the plasma sample at 37 ℃, and pre-warming CaCl 2 at 37 ℃;
② . Mixing the factor XI measuring reagent and the diluted plasma sample in a volume ratio of 1:1, mixing at 37 ℃ and incubating for 0.5-2 minutes;
③ . Adding APTT reagent and mixing the diluted plasma sample in a volume ratio of 1:1, mixing at 37 ℃ and incubating for 0.5-2 minutes;
④ . Adding CaCl 2 reagent and mixing the diluted plasma sample in a volume ratio of 1:1, and reading absorbance value of the sample at 405nm after 2 minutes of action at 37 ℃;
⑤ . The activity of factor XI in plasma samples was calculated from known standard curves.
The invention provides a protective agent comprising a buffer solution, a freeze-drying protective agent, a surfactant, a preservative and inorganic salt, factor XI deficient plasma comprising human factor XI plasma and the protective agent, and application of the factor XI deficient plasma in preparing a blood coagulation factor activity detection reagent or a kit. Compared with the prior art, the protective agent provided by the invention can effectively ensure the stability and activity of the protein in human factor XI blood plasma, and further improve the product performance of the human factor XI blood plasma. The protective agent disclosed by the invention is prepared from trehalose, glycine and dextran-40 which are used as freeze-drying protective agents, so that the stability of plasma proteins in plasma in a freeze-drying process and the stability of freeze-dried products after re-dissolution can be effectively protected; poloxamer 188 is used as a surfactant to further protect the proteins in the plasma from inactivation by the lyophilization process. The factor XI deficient plasma provided by the invention is suitable for most of the common full-automatic coagulation analyzers in the market.
Drawings
FIG. 1 changes in clotting factor II activity in matrix plasma;
FIG. 2 shows the variation of clotting factor V activity in matrix plasma;
FIG. 3 shows the change in clotting factor VII activity in matrix plasma;
FIG. 4 shows the change in clotting factor VIII activity in matrix plasma;
FIG. 5 shows the change in clotting factor IX activity in matrix plasma;
FIG. 6 shows the variation of clotting factor X activity in matrix plasma;
FIG. 7 shows the change in coagulation factor XII activity in matrix plasma;
FIG. 8 shows the variation of the clotting factor FIB content in the matrix plasma;
FIG. 9 shows a correlation analysis of the detection results of the kit of the present invention with the Siemens kit at CS 2400;
FIG. 10 shows analysis of correlation of detection results of the inventive kit and STAGO kit on STA-R event;
fig. 11 shows the correlation analysis of the detection results of the kit of the invention and the IL kit on acltop 750.
Detailed Description
The invention provides factor XI deficiency plasma protectant and application thereof, and one skilled in the art can properly improve the process parameters by referring to the content of the text. It is expressly noted that all such similar substitutions and modifications will be apparent to those skilled in the art, and are deemed to be included in the present invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the relevant art that the invention can be practiced and practiced with modification and alteration and combination of the methods and applications herein without departing from the spirit and scope of the invention.
The invention provides a protective agent, which comprises buffer solution, freeze-drying protective agent, surfactant, preservative and inorganic salt, wherein,
The buffer solution is at least one selected from HEPES buffer solution, tris buffer solution and phosphate buffer solution;
The protective agent is at least one selected from sucrose, mannitol, sorbitol, glycine, dextran-40 and trehalose;
the surfactant is at least one selected from poloxamer 188 and sodium cholate;
The preservative is at least one selected from NaN 3, merthiolate and ciprofloxacin;
the inorganic salt is at least one selected from sodium chloride and potassium chloride.
The test materials adopted by the invention are all common commercial products and can be purchased in the market. The invention is further illustrated by the following examples:
EXAMPLE 1 preparation of the kit of the invention for factor XI deficient plasma
The invention provides a formula for preparing a factor XI assay kit by using human factor XI-deficient plasma, which adopts the following technical scheme:
The manufacturer of the human factor XI blood plasma used in the research and development process of the kit is German Biomex GmbH, and the pH value of the protective agent is regulated to 7.8 and then added into the human factor XI blood plasma to be fully and uniformly mixed. The formulation of the protective agent of the kit is shown in table 1, and the volume ratio of the protective agent to plasma is 2:8.
TABLE 1 protectant formulation table (Experimental group)
Table 2 protective agent formulation table (control group)
EXAMPLE 2 investigation of the ratio of the protective agent to plasma of the kit of the invention
The ratio of the protective agent to the plasma in the kit is mainly set to 3 gradients, namely 1:9, 2:8 and 3:7, so as to explore the influence of the ratio of the protective agent to the plasma on the accuracy of the measurement value of the kit. The standard human plasma (target value: 91%) of Siemens is accurately detected by taking commercial products and freeze-dried products of each experimental group, and the detection results are summarized and the relative deviation between the detection results and the standard human plasma target value is calculated. The results are shown in Table 3, and the relative deviation of the activity values from the target values for the standard human plasma measured by all experimental groups was smaller than that of the commercial kit. Experimental results show that the ratio of the protective agent to the blood plasma has little influence on the accuracy of the measured value of the blood plasma, but when the ratio is 2:8, the relative deviation between the measured value and the target value is the smallest, and the ratio of the protective agent to the blood plasma in the kit is (1-3) (7-9), preferably 2:8.
TABLE 3 accuracy test results
Note that: relative deviation = (test value-calibrator target value)/calibrator target value x 100%
EXAMPLE 3 stability study of the Components of the kit of the invention
The substrate plasma was subjected to coagulation factor assay (II, V, VII, VIII, IX, X, XII) and FIB content assay, and after plasma was prepared as in example 1, stability assay was performed. Blood coagulation factor and FIB detection were performed on factor XI deficient plasma before and after lyophilization, respectively, and the average value was taken three times for each detection, and the statistical analysis (t-test) was performed on the detected data, and the results are shown in tables 4 to 11. The results show that the activity and the FIB content of each blood coagulation factor in the blood plasma of the control group are reduced to different degrees, and the activity and the FIB content of each blood coagulation factor in the blood plasma before and after freeze-drying of the kit (experimental group) have no obvious change, so that the components of the kit (experimental group) can effectively protect the blood coagulation factors in the blood plasma from the influence of the freeze-drying process; after the freeze-dried product of the kit (experimental group) is redissolved, the activity of each blood coagulation factor has no obvious change in the continuous 5-day test, which indicates that the combination of the components of the protective agent of the kit can effectively stabilize the enzyme activities of each blood coagulation factor and FIB after the plasma is redissolved. The comparison of the experimental group and the control group 1-8 shows that any one of the components of the trehalose, the glycine and the dextran-40 is deleted or replaced, the freeze-drying protection effect is reduced to different degrees, which indicates that the trehalose, the glycine and the dextran-40 are used as the protecting agent together, and the stability of plasma proteins in plasma in the freeze-drying process and the stability of the freeze-dried product after re-dissolution can be effectively protected. Comparison of the experimental group with the control group 9 shows that the addition of poloxamer 188 can further protect the proteins in the plasma from inactivation caused by the lyophilization process.
TABLE 4 measurement of coagulation factor II Activity
TABLE 5 measurement of coagulation factor V Activity
TABLE 6 measurement of factor VII Activity
TABLE 7 measurement of factor VIII Activity
TABLE 8 measurement of factor IX Activity
TABLE 9 measurement of coagulation factor X Activity
TABLE 10 measurement of factor XII Activity
TABLE 11 FIB content determination results
Example 4 concentration of major components of protective agent in the kit of the present invention the major components of the protective agent were set to 3 concentrations, respectively, and the set was set by an orthogonal method (as in table 12) to investigate the effect of the concentration of each component of the protective agent on the reproducibility of the kit. And repeatedly detecting the normal range fixed value Plasma (Control Plasma N) and the pathological range fixed value Plasma (Control Plasma P) by taking commercially available products and freeze-dried products of each experimental group. The measurement results were collected and the Coefficient of Variation (CV) was calculated. The results are shown in Table 12, and the Coefficient of Variation (CV) of the normal range and pathological range plasma was smaller than that of the commercial kit (5.18%, 8.42%). Meanwhile, the experimental results of experimental group 5 are superior to other experimental groups. In summary, the kit has good repeatability of detection results when the concentration of trehalose in the kit protective agent component is 10-50g/L, the concentration of glycine is 10-100g/L, the concentration of dextran-40 is 10-50g/L, the concentration of poloxamer 188 is 1-5g/L, and the kit is most preferable when the concentration of trehalose is 20g/L, the concentration of glycine is 50g/L, the concentration of dextran-40 is 20g/L, and the concentration of poloxamer 188 is2 g/L.
TABLE 12 repeatability test results
Example 5 applicability of the kit of the present invention to a coagulation analyzer which is mainstream in the market
(1) Application of the kit of the invention to CS2400
A total of 57 blood samples were randomly drawn from hospitalization and outpatient clinics at the Shanghai university of transportation medical institute affiliated Ruijin Hospital and at the Shanghai university of traditional Chinese medicine affiliated Longhua Hospital. Uniformly mixing blood with 0.109mol/L sodium citrate anticoagulation solution according to the ratio of 9:1, centrifuging at 2500r/min for 15 minutes, and separating to obtain plasma. The samples were measured on CS2400 using the kit of the present invention obtained in example 1 and the Siemens factor XI activity measurement kit (clotting method), respectively, and correlation coefficients of the two were calculated and subjected to linear regression. The results show that the correlation coefficient of the two kits, γ= 0.9955, and the linear regression equation, y= -0.1139+1.0231x, see fig. 9.
According to the requirements of the American Clinical Laboratory Standardization Institute (CLSI) document (gamma > 0.975), the detection data of the kit provided by the invention and the French STAGO company import kit have good consistency.
(2) Application of the kit in STA-R Evolution
Blood samples were randomly drawn from hospitalization and outpatient clinics at the Shanghai university of transportation medical institute affiliated Ruijin Hospital and the Shanghai university of traditional Chinese medicine affiliated Longhua Hospital for 50 copies. Uniformly mixing blood with 0.109mol/L sodium citrate anticoagulation solution according to the ratio of 9:1, centrifuging at 2500r/min for 15 minutes, and separating to obtain plasma. The correlation coefficients of the kit of the present invention obtained in example 1 and the Factor XI (FXI) measurement kit (clotting method) from STAGO were calculated by measuring the samples on STA-R Evolution, respectively, and performing linear regression. The results show that the correlation coefficient γ= 0.9936 for both kits, the linear regression equation is y=0.2994+0.9818 x, see fig. 10.
According to the requirements of the American Clinical Laboratory Standardization Institute (CLSI) document (gamma > 0.975), the detection data of the kit provided by the invention and the detection data of the STAGO company imported kit are in good consistency.
(3) Application of the kit of the invention to ACL TOP 750
Blood samples were randomly drawn from hospitalization and outpatient clinics at the Shanghai university of transportation medical institute affiliated Ruijin Hospital and the Shanghai university of traditional Chinese medicine affiliated Longhua Hospital for a total of 85. Uniformly mixing blood with 0.109mol/L sodium citrate anticoagulation solution according to the ratio of 9:1, centrifuging at 2500r/min for 15 minutes, and separating to obtain plasma. The correlation coefficients of the two were calculated and subjected to linear regression by measuring the samples on ACL TOP 750 using the kit of the present invention obtained in example 1 and the IL company Factor XI DEFICIENT PIASMA kit, respectively. The results show that the correlation coefficient of the two kits, γ= 0.9921, and the linear regression equation, y= -0.9793+1.0233x, see fig. 11.
The test data of the kit of the invention and the imported kit of the US IL company have good consistency according to the requirements of the American Clinical Laboratory Standardization Institute (CLSI) document (gamma > 0.975).
In conclusion, the kit disclosed by the invention can be suitable for most of full-automatic coagulation analyzers commonly used in the market.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (6)
1. The protective agent is characterized by comprising water, 240g/L HEPES buffer solution, 20g/L trehalose, 50g/L glycine, 20g/L dextran-40, 2g/L poloxamer 188, 2.5g/L ciprofloxacin and 0.2g/L sodium chloride, wherein the pH value of the protective agent is 7.8.
2. Use of the protective agent of claim 1 for the preparation of factor XI deficient plasma or a kit comprising factor XI deficient plasma.
3. Factor XI deficient plasma or a kit comprising factor XI deficient plasma, comprising human factor XI plasma and a protective agent according to claim 1.
4. The factor XI deficient plasma or kit comprising factor XI deficient plasma according to claim 3 wherein the volume ratio of the protective agent to the human factor XI deficient plasma is (1-3): 7-9.
5. The factor XI deficient plasma or kit comprising factor XI deficient plasma according to claim 4 wherein the volume ratio of the protective agent to the human factor XI deficient plasma is 2:8.
6. Use of the factor XI deficient plasma or a kit comprising factor XI deficient plasma according to any one of claims 3 to 5 in the preparation of a clotting factor activity detection reagent or kit.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310392199.6A CN116410258B (en) | 2023-04-13 | 2023-04-13 | Factor XI deficiency plasma protective agent and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310392199.6A CN116410258B (en) | 2023-04-13 | 2023-04-13 | Factor XI deficiency plasma protective agent and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116410258A CN116410258A (en) | 2023-07-11 |
| CN116410258B true CN116410258B (en) | 2024-07-19 |
Family
ID=87051030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310392199.6A Active CN116410258B (en) | 2023-04-13 | 2023-04-13 | Factor XI deficiency plasma protective agent and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116410258B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114617903B (en) * | 2022-03-15 | 2024-05-24 | 中国人民解放军总医院第一医学中心 | Composition for freeze-drying blood plasma and application thereof |
| CN117180441A (en) * | 2023-10-11 | 2023-12-08 | 北京朴汇细胞生物科技有限公司 | Platelet dehydration and drying protective agent, platelet dehydration and drying preparation and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115327128A (en) * | 2022-07-01 | 2022-11-11 | 深圳市帝迈生物技术有限公司 | VIII factor activity determination kit and preparation method thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3005019B2 (en) * | 1990-05-25 | 2000-01-31 | 旭メディカル株式会社 | Kit and method for preparing cryopreserved blood |
| US7931919B2 (en) * | 2005-08-12 | 2011-04-26 | The United States Of America As Represented By The Secretary Of The Army | Method of producing glycine-stabilized, lyophilized plasma |
| CN104231073B (en) * | 2014-09-25 | 2017-01-25 | 广东双林生物制药有限公司 | Preparation method of human coagulation factor VIII |
| CN104623701B (en) * | 2014-12-26 | 2017-12-29 | 四川远大蜀阳药业股份有限公司 | Parvovirus method and the preparation of acquisition in a kind of effectively inactivation PCC |
| CN113227150B (en) * | 2018-08-09 | 2023-07-28 | 上海仁会生物制药股份有限公司 | Anticoagulant factor XI antibodies |
| CN112481355B (en) * | 2020-11-16 | 2023-05-30 | 武汉市长立生物技术有限责任公司 | Liquid prothrombin time determination kit and preparation method thereof |
| CN115327120A (en) * | 2022-07-01 | 2022-11-11 | 深圳市帝迈生物技术有限公司 | VII factor activity determination kit and preparation method thereof |
-
2023
- 2023-04-13 CN CN202310392199.6A patent/CN116410258B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115327128A (en) * | 2022-07-01 | 2022-11-11 | 深圳市帝迈生物技术有限公司 | VIII factor activity determination kit and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 陈玉祥等.《分子药剂学》.湖南师范大学出版社,2009,第109-111页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116410258A (en) | 2023-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN116410258B (en) | Factor XI deficiency plasma protective agent and application thereof | |
| Siegelman et al. | Investigation of serum trypsin and related substances: I. The quantitative demonstration of trypsinlike activity in human blood serum by a micromethod | |
| US5525477A (en) | Method for diagnosing blood clotting disorders | |
| Kachhawa et al. | Study of the stability of various biochemical analytes in samples stored at different predefined storage conditions at an accredited laboratory of India | |
| JP2955345B2 (en) | Endotoxin kinetic assay using Limulus amoebocyte lysate and chromogenic substrate | |
| CN109239061A (en) | A kind of liquid-type Antiprothrombin antibodies assay kit | |
| CN107748267A (en) | One kind measure activated partial thromboplastin time（APTT）Kit | |
| BR112014031934B1 (en) | euglobulin-based method to determine the biological activity of defibrotide | |
| CN107153043A (en) | A kind of liquid instant Antiprothrombin antibodies determine reagent | |
| CN105548560A (en) | A serum albumin detecting reagent and a serum albumin detecting method | |
| Potze et al. | Preserved clot formation detected by the Thrombodynamics analyzer in patients with cirrhosis | |
| CN110988358A (en) | High-sensitivity human urine α 2-macroglobulin detection kit | |
| CN110714051B (en) | Protein C activity determination kit | |
| CN114200122A (en) | Freeze-dried reagent ball for uric acid detection, configuration method thereof and microfluidic detection chip | |
| WO2001023536A1 (en) | Means of stabilizing thrombin and compositions | |
| WO2021000654A1 (en) | Method for detecting heparin or heparin-like substances in blood and kit | |
| Carlton et al. | Biomarkers in pediatric acute respiratory distress syndrome | |
| CN113341164B (en) | Activated partial thromboplastin time determination reagent card and preparation method and application thereof | |
| CN111175515B (en) | Two-in-one quality control substance of serum amyloid A and serum amyloid C reactive protein and preparation method thereof | |
| JPH04501809A (en) | Factor IX chromogenic assay | |
| van den Besselaar et al. | Influence of blood collection systems on the prothrombin time and international sensitivity index determined with human and rabbit thromboplastin reagents | |
| JP5425062B2 (en) | Method for measuring glycoalbumin and the like using a control sample containing D-mannitol | |
| Jensen et al. | Influence of freeze-drying on the clotting properties of fibrinogen in plasma | |
| CN117554605B (en) | Quality control product for detecting ADAMTS13 as well as preparation method and application thereof | |
| Lambert et al. | The tri-F titer: a rapid test for estimation of plasma fibrinogen and detection of fibrinolysis, fibrin (ogen) split products, and heparin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |