CA1040562A - Methodes pour purifier les preparations contenant de l'urokinase - Google Patents

Methodes pour purifier les preparations contenant de l'urokinase

Info

Publication number: CA1040562A
Authority: CA; Canada
Prior art keywords: solution; urokinase; micromhos; ammonium sulphate; proteins
Prior art date: 1972-09-22
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.): Expired

Application number

CA240,777A

Other languages

English (en)

Inventor

Edmond G. Vairel

Jean Goulay

Jean Choay

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Choay SA

Original Assignee

Choay SA

Priority date (The priority date 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 date listed.)

1972-09-22

Filing date

1975-12-01

Publication date

1978-10-17

1972-09-22 Priority claimed from CA152,328A external-priority patent/CA986013A/en

1975-12-01 Application filed by Choay SA filed Critical Choay SA

1978-10-17 Application granted granted Critical

1978-10-17 Publication of CA1040562A publication Critical patent/CA1040562A/fr

Status Expired legal-status Critical Current

Links

102000003990 Urokinase-type plasminogen activator Human genes 0.000 title claims abstract description 124
108090000435 Urokinase-type plasminogen activator Proteins 0.000 title claims abstract description 124
229960005356 urokinase Drugs 0.000 title claims abstract description 124
238000000034 method Methods 0.000 title claims abstract description 34
238000002360 preparation method Methods 0.000 title description 10
102000004169 proteins and genes Human genes 0.000 claims abstract description 42
108090000623 proteins and genes Proteins 0.000 claims abstract description 42
239000002244 precipitate Substances 0.000 claims abstract description 33
239000000126 substance Substances 0.000 claims abstract description 24
230000001698 pyrogenic effect Effects 0.000 claims abstract description 23
239000007788 liquid Substances 0.000 claims abstract description 19
239000006228 supernatant Substances 0.000 claims abstract description 14
239000000243 solution Substances 0.000 claims description 129
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 34
229910052921 ammonium sulfate Inorganic materials 0.000 claims description 32
239000001166 ammonium sulphate Substances 0.000 claims description 32
235000011130 ammonium sulphate Nutrition 0.000 claims description 32
239000011347 resin Substances 0.000 claims description 29
229920005989 resin Polymers 0.000 claims description 29
230000000694 effects Effects 0.000 claims description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
238000002270 exclusion chromatography Methods 0.000 claims description 17
239000005995 Aluminium silicate Substances 0.000 claims description 14
235000012211 aluminium silicate Nutrition 0.000 claims description 14
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 14
238000001914 filtration Methods 0.000 claims description 13
210000002700 urine Anatomy 0.000 claims description 13
238000005406 washing Methods 0.000 claims description 13
GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 claims description 12
229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 10
239000001768 carboxy methyl cellulose Substances 0.000 claims description 10
235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 10
239000008112 carboxymethyl-cellulose Substances 0.000 claims description 10
238000000746 purification Methods 0.000 claims description 10
238000004587 chromatography analysis Methods 0.000 claims description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
229910019142 PO4 Inorganic materials 0.000 claims description 6
239000003795 chemical substances by application Substances 0.000 claims description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 6
239000010452 phosphate Substances 0.000 claims description 6
238000001556 precipitation Methods 0.000 claims description 6
238000000502 dialysis Methods 0.000 claims description 5
239000008363 phosphate buffer Substances 0.000 claims description 5
230000000717 retained effect Effects 0.000 claims description 5
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
239000002671 adjuvant Substances 0.000 claims description 4
235000019270 ammonium chloride Nutrition 0.000 claims description 4
238000000605 extraction Methods 0.000 claims description 4
239000008103 glucose Substances 0.000 claims description 4
229910021529 ammonia Inorganic materials 0.000 claims description 3
230000001376 precipitating effect Effects 0.000 claims description 2
238000005185 salting out Methods 0.000 claims description 2
238000009738 saturating Methods 0.000 claims description 2
239000012461 cellulose resin Substances 0.000 claims 4
238000011282 treatment Methods 0.000 abstract description 6
208000011580 syndromic disease Diseases 0.000 abstract description 3
230000009424 thromboembolic effect Effects 0.000 abstract description 2
235000018102 proteins Nutrition 0.000 description 33
238000007792 addition Methods 0.000 description 14
238000010521 absorption reaction Methods 0.000 description 13
239000000725 suspension Substances 0.000 description 12
239000000706 filtrate Substances 0.000 description 10
229940105329 carboxymethylcellulose Drugs 0.000 description 8
238000005119 centrifugation Methods 0.000 description 7
239000012153 distilled water Substances 0.000 description 7
241000283973 Oryctolagus cuniculus Species 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
238000013019 agitation Methods 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
238000010828 elution Methods 0.000 description 6
238000005755 formation reaction Methods 0.000 description 6
239000000203 mixture Substances 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
239000012535 impurity Substances 0.000 description 5
239000000843 powder Substances 0.000 description 5
238000011082 depyrogenation Methods 0.000 description 4
230000007717 exclusion Effects 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
239000007853 buffer solution Substances 0.000 description 3
229920002678 cellulose Polymers 0.000 description 3
239000001913 cellulose Substances 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
229940088598 enzyme Drugs 0.000 description 3
210000002196 fr. b Anatomy 0.000 description 3
210000003918 fraction a Anatomy 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
229910021653 sulphate ion Inorganic materials 0.000 description 3
239000001117 sulphuric acid Substances 0.000 description 3
235000011149 sulphuric acid Nutrition 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
102000013566 Plasminogen Human genes 0.000 description 2
108010051456 Plasminogen Proteins 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
229920001429 chelating resin Polymers 0.000 description 2
230000008030 elimination Effects 0.000 description 2
238000003379 elimination reaction Methods 0.000 description 2
210000000540 fraction c Anatomy 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
-1 oxycellulose Chemical compound 0.000 description 2
229910052573 porcelain Inorganic materials 0.000 description 2
229940070376 protein Drugs 0.000 description 2
230000006920 protein precipitation Effects 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000000926 separation method Methods 0.000 description 2
SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 description 1
DPEYHNFHDIXMNV-UHFFFAOYSA-N (9-amino-3-bicyclo[3.3.1]nonanyl)-(4-benzyl-5-methyl-1,4-diazepan-1-yl)methanone dihydrochloride Chemical compound Cl.Cl.CC1CCN(CCN1Cc1ccccc1)C(=O)C1CC2CCCC(C1)C2N DPEYHNFHDIXMNV-UHFFFAOYSA-N 0.000 description 1
JVIPLYCGEZUBIO-UHFFFAOYSA-N 2-(4-fluorophenyl)-1,3-dioxoisoindole-5-carboxylic acid Chemical compound O=C1C2=CC(C(=O)O)=CC=C2C(=O)N1C1=CC=C(F)C=C1 JVIPLYCGEZUBIO-UHFFFAOYSA-N 0.000 description 1
IWSZDQRGNFLMJS-UHFFFAOYSA-N 2-(dibutylamino)ethanol Chemical compound CCCCN(CCO)CCCC IWSZDQRGNFLMJS-UHFFFAOYSA-N 0.000 description 1
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
VZEZONWRBFJJMZ-UHFFFAOYSA-N 3-allyl-2-[2-(diethylamino)ethoxy]benzaldehyde Chemical compound CCN(CC)CCOC1=C(CC=C)C=CC=C1C=O VZEZONWRBFJJMZ-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
206010002199 Anaphylactic shock Diseases 0.000 description 1
241000237074 Centris Species 0.000 description 1
241000511343 Chondrostoma nasus Species 0.000 description 1
102000009123 Fibrin Human genes 0.000 description 1
108010073385 Fibrin Proteins 0.000 description 1
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
206010020843 Hyperthermia Diseases 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
241000219289 Silene Species 0.000 description 1
230000001133 acceleration Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000004075 alteration Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
208000003455 anaphylaxis Diseases 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
238000005341 cation exchange Methods 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
230000001112 coagulating effect Effects 0.000 description 1
238000005345 coagulation Methods 0.000 description 1
230000015271 coagulation Effects 0.000 description 1
MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
235000019800 disodium phosphate Nutrition 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000003073 embolic effect Effects 0.000 description 1
239000004744 fabric Substances 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
239000003527 fibrinolytic agent Substances 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
238000007429 general method Methods 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
230000036031 hyperthermia Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
229940012957 plasmin Drugs 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
230000009291 secondary effect Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
239000012064 sodium phosphate buffer Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
229920002994 synthetic fiber Polymers 0.000 description 1
235000018553 tannin Nutrition 0.000 description 1
229920001864 tannin Polymers 0.000 description 1
239000001648 tannin Substances 0.000 description 1
229960000103 thrombolytic agent Drugs 0.000 description 1
230000009466 transformation Effects 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
229960004319 trichloroacetic acid Drugs 0.000 description 1
230000002792 vascular Effects 0.000 description 1

Landscapes

Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Enzymes And Modification Thereof (AREA)

CA240,777A 1972-09-22 1975-12-01 Methodes pour purifier les preparations contenant de l'urokinase Expired CA1040562A (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA152,328A CA986013A (en)	1971-09-24	1972-09-22	Methods for preparing depyrogenising and stabilising urokinase and compositions obtained thereby

Publications (1)

Publication Number	Publication Date
CA1040562A true CA1040562A (fr)	1978-10-17

Family

ID=4094499

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA240,777A Expired CA1040562A (fr)	1972-09-22	1975-12-01	Methodes pour purifier les preparations contenant de l'urokinase

Country Status (1)

Country	Link
CA (1)	CA1040562A (fr)

1975
- 1975-12-01 CA CA240,777A patent/CA1040562A/fr not_active Expired

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US4029767A (en)	1977-06-14	Pharmaceutical compositions of stable urokinase-heparin complexes and methods for use thereof
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US4065445A (en)	1977-12-27	Pregnancy-specific β1 -glycoprotein and process for isolating it
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US5760183A (en)	1998-06-02	Process for the manufacture of very high-purity antithaemophilic factor (FVIIIC), and von Willebrand factor, and pharmaceutical compositions containing same
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US3926727A (en)	1975-12-16	Urokinase preparations
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GB2038337A (en)	1980-07-23	Process which comprises separation of urokinases having different molecular weights
US4873222A (en)	1989-10-10	Placenta-derived anticoagulating substance
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