CA1041090A - Procede de purification de l'insuline - Google Patents

Procede de purification de l'insuline

Info

Publication number: CA1041090A
Authority: CA; Canada
Prior art keywords: insulin; gel; column; range; acetic acid
Prior art date: 1975-01-29
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

CA218,971A

Other languages

English (en)

Other versions

CA218971S (en

Inventor

Richard L. Jackson

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.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1975-01-29

Filing date

1975-01-29

Publication date

1978-10-24

1975-01-29 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1975-01-29 Priority to CA218,971A priority Critical patent/CA1041090A/fr

1978-10-24 Application granted granted Critical

1978-10-24 Publication of CA1041090A publication Critical patent/CA1041090A/fr

Status Expired legal-status Critical Current

Links

NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 260
102000004877 Insulin Human genes 0.000 title claims abstract description 141
108090001061 Insulin Proteins 0.000 title claims abstract description 141
229940125396 insulin Drugs 0.000 title claims abstract description 130
238000000034 method Methods 0.000 title claims abstract description 53
229910052783 alkali metal Inorganic materials 0.000 claims abstract description 16
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims abstract description 15
150000001340 alkali metals Chemical class 0.000 claims abstract description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 74
239000000243 solution Substances 0.000 claims description 27
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
238000010828 elution Methods 0.000 claims description 12
229920005654 Sephadex Polymers 0.000 claims description 9
238000011068 loading method Methods 0.000 claims description 8
239000002245 particle Substances 0.000 claims description 8
239000011780 sodium chloride Substances 0.000 claims description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
235000015278 beef Nutrition 0.000 claims description 6
230000008961 swelling Effects 0.000 claims description 6
229910017053 inorganic salt Inorganic materials 0.000 claims description 5
235000015277 pork Nutrition 0.000 claims description 5
239000007864 aqueous solution Substances 0.000 claims description 4
238000012856 packing Methods 0.000 claims description 4
229920002307 Dextran Polymers 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims 2
238000002523 gelfiltration Methods 0.000 abstract description 11
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 32
229910052725 zinc Inorganic materials 0.000 description 32
239000011701 zinc Substances 0.000 description 32
239000000499 gel Substances 0.000 description 19
235000011054 acetic acid Nutrition 0.000 description 18
235000018102 proteins Nutrition 0.000 description 17
102000004169 proteins and genes Human genes 0.000 description 17
108090000623 proteins and genes Proteins 0.000 description 17
239000002609 medium Substances 0.000 description 13
239000002904 solvent Substances 0.000 description 12
235000002639 sodium chloride Nutrition 0.000 description 10
108010076181 Proinsulin Proteins 0.000 description 9
238000001556 precipitation Methods 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
238000000746 purification Methods 0.000 description 7
238000000926 separation method Methods 0.000 description 7
239000007787 solid Substances 0.000 description 7
210000000496 pancreas Anatomy 0.000 description 6
239000011148 porous material Substances 0.000 description 6
238000005185 salting out Methods 0.000 description 6
108010007568 Protamines Proteins 0.000 description 5
102000007327 Protamines Human genes 0.000 description 5
238000010586 diagram Methods 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000007863 gel particle Substances 0.000 description 5
229940048914 protamine Drugs 0.000 description 5
238000011084 recovery Methods 0.000 description 5
101710114386 Insulin-like protein Proteins 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
102000005237 Isophane Insulin Human genes 0.000 description 3
108010081368 Isophane Insulin Proteins 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000012736 aqueous medium Substances 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
206010012601 diabetes mellitus Diseases 0.000 description 3
239000000284 extract Substances 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000012535 impurity Substances 0.000 description 3
239000004026 insulin derivative Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
230000007935 neutral effect Effects 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000011800 void material Substances 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
102000003670 Carboxypeptidase B Human genes 0.000 description 2
108090000087 Carboxypeptidase B Proteins 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
230000005526 G1 to G0 transition Effects 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
239000000872 buffer Substances 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
230000007423 decrease Effects 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
229940088598 enzyme Drugs 0.000 description 2
239000012847 fine chemical Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
210000004907 gland Anatomy 0.000 description 2
230000002218 hypoglycaemic effect Effects 0.000 description 2
238000004255 ion exchange chromatography Methods 0.000 description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
238000002955 isolation Methods 0.000 description 2
229940006445 isophane insulin Drugs 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
239000000203 mixture Substances 0.000 description 2
ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000002335 preservative effect Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
OMDQUFIYNPYJFM-XKDAHURESA-N (2r,3r,4s,5r,6s)-2-(hydroxymethyl)-6-[[(2r,3s,4r,5s,6r)-4,5,6-trihydroxy-3-[(2s,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]oxane-3,4,5-triol 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]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@H](O)[C@H](O)O1 OMDQUFIYNPYJFM-XKDAHURESA-N 0.000 description 1
XRBWKWGATZNBFW-UHFFFAOYSA-N 2-[2-(2-ethenoxyethoxy)ethoxy]ethanol Chemical compound OCCOCCOCCOC=C XRBWKWGATZNBFW-UHFFFAOYSA-N 0.000 description 1
FZIPCQLKPTZZIM-UHFFFAOYSA-N 2-oxidanylpropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O FZIPCQLKPTZZIM-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
101800000263 Acidic protein Proteins 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
241000199897 Alaria esculenta Species 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
108090000317 Chymotrypsin Proteins 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
206010013457 Dissociation Diseases 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
229920000926 Galactomannan Polymers 0.000 description 1
102000051325 Glucagon Human genes 0.000 description 1
108060003199 Glucagon 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
235000019759 Maize starch Nutrition 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
108090000631 Trypsin Proteins 0.000 description 1
102000004142 Trypsin Human genes 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000008272 agar Substances 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
230000000676 anti-immunogenic effect Effects 0.000 description 1
230000000890 antigenic effect Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3N=CN=C3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229960002376 chymotrypsin Drugs 0.000 description 1
239000007979 citrate buffer Substances 0.000 description 1
238000010960 commercial process Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
239000000287 crude extract Substances 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
108700022849 desamido- insulin Proteins 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
208000018459 dissociative disease Diseases 0.000 description 1
238000009826 distribution Methods 0.000 description 1
-1 e.g. Proteins 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
238000002270 exclusion chromatography Methods 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000000727 fraction Substances 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
238000001641 gel filtration chromatography Methods 0.000 description 1
238000005227 gel permeation chromatography Methods 0.000 description 1
102000018146 globin Human genes 0.000 description 1
108060003196 globin Proteins 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
235000011167 hydrochloric acid Nutrition 0.000 description 1
238000010324 immunological assay Methods 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
108010066090 neutral insulin Proteins 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
210000004923 pancreatic tissue Anatomy 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
229940070376 protein Drugs 0.000 description 1
235000004252 protein component Nutrition 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000009938 salting Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1

Landscapes

Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA218,971A 1975-01-29 1975-01-29 Procede de purification de l'insuline Expired CA1041090A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA218,971A CA1041090A (fr)	1975-01-29	1975-01-29	Procede de purification de l'insuline

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA218,971A CA1041090A (fr)	1975-01-29	1975-01-29	Procede de purification de l'insuline

Publications (1)

Publication Number	Publication Date
CA1041090A true CA1041090A (fr)	1978-10-24

Family

ID=4102167

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA218,971A Expired CA1041090A (fr)	1975-01-29	1975-01-29	Procede de purification de l'insuline

Country Status (1)

Country	Link
CA (1)	CA1041090A (fr)

1975
- 1975-01-29 CA CA218,971A patent/CA1041090A/fr not_active Expired

Publication	Publication Date	Title
US3876623A (en)	1975-04-08	Process for purifying insulin
Davison et al.	1974	The protein subunit of calf brain neurofilament
Tarr et al.	1983	Reverse-phase high-performance liquid chromatography of hydrophobic proteins and fragments thereof
Porath	1959	Fractionation of polypeptides and proteins on dextran gels
Carra	1965	Purification and N-terminal analyses of algal biliproteins
Dotimas et al.	1987	Isolation and structure analysis of bee venom mast cell degranulating peptide
US6180757B1 (en)	2001-01-30	Process for the separation of proteins using a CA++ containing eluant
Porath et al.	1962	Gel filtration of posterior pituitary hormones
US3878186A (en)	1975-04-15	Process for purifying insulin
Free et al.	1966	Separation and properties of multiple components of bovine growth hormone
US5290920A (en)	1994-03-01	Method of purifying human epidermal growth factor
Scholz et al.	1974	Studies on Seed Globulins from Legumes: I. Separation and Purification of Legumin and Vicilin from Vicia faba L. by Zone Precipitation
KR0178274B1 (ko)	1999-04-01	재조합 소마토트로핀의 회수방법
WO1990000568A1 (fr)	1990-01-25	Nouveau polypeptide et methode de production
CA1041090A (fr)	1978-10-24	Procede de purification de l'insuline
EP0013826A1 (fr)	1980-08-06	Procédé pour purifier l'insuline et insuline ainsi préparée
JPH02209896A (ja)	1990-08-21	還元型の非グリコシル化組換ヒトｉｌ↓２、その取得方法、及び薬物としてのその使用
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