CA1112639A - Mono-insulin and method of preparing the same - Google Patents
Mono-insulin and method of preparing the sameInfo
- Publication number
- CA1112639A CA1112639A CA269,730A CA269730A CA1112639A CA 1112639 A CA1112639 A CA 1112639A CA 269730 A CA269730 A CA 269730A CA 1112639 A CA1112639 A CA 1112639A
- Authority
- CA
- Canada
- Prior art keywords
- insulin
- extract
- process according
- reverse osmosis
- substances
- 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.)
- Expired
Links
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Substances 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 267
- 229940125396 insulin Drugs 0.000 title claims abstract description 136
- 238000000034 method Methods 0.000 title claims abstract description 69
- 102000004877 Insulin Human genes 0.000 claims abstract description 133
- 108090001061 Insulin Proteins 0.000 claims abstract description 133
- 239000000284 extract Substances 0.000 claims abstract description 57
- 230000008569 process Effects 0.000 claims abstract description 41
- 239000000126 substance Substances 0.000 claims abstract description 22
- 238000000926 separation method Methods 0.000 claims abstract description 19
- 239000012535 impurity Substances 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 16
- 238000000746 purification Methods 0.000 claims abstract description 14
- 238000001223 reverse osmosis Methods 0.000 claims abstract description 14
- 238000005342 ion exchange Methods 0.000 claims abstract description 12
- 210000000496 pancreas Anatomy 0.000 claims abstract description 10
- 238000001556 precipitation Methods 0.000 claims abstract description 10
- 238000004040 coloring Methods 0.000 claims abstract description 8
- 210000004907 gland Anatomy 0.000 claims abstract description 7
- 238000001816 cooling Methods 0.000 claims abstract description 5
- 238000011084 recovery Methods 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 229910021645 metal ion Inorganic materials 0.000 claims abstract 3
- 150000002500 ions Chemical class 0.000 claims description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 35
- 239000012528 membrane Substances 0.000 claims description 12
- 230000001476 alcoholic effect Effects 0.000 claims description 8
- 239000012141 concentrate Substances 0.000 claims description 7
- 229920002401 polyacrylamide Polymers 0.000 claims description 7
- 239000002808 molecular sieve Substances 0.000 claims description 5
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 claims description 5
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 5
- 238000004440 column chromatography Methods 0.000 claims description 4
- 238000002523 gelfiltration Methods 0.000 claims description 4
- 239000007791 liquid phase Substances 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 238000010923 batch production Methods 0.000 claims description 2
- 230000001627 detrimental effect Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 8
- 230000008859 change Effects 0.000 abstract description 4
- 238000012545 processing Methods 0.000 abstract description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 abstract description 2
- 238000001502 gel electrophoresis Methods 0.000 abstract description 2
- 150000001408 amides Chemical class 0.000 abstract 1
- 235000019441 ethanol Nutrition 0.000 description 19
- 210000004379 membrane Anatomy 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 9
- 239000000872 buffer Substances 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 238000001179 sorption measurement Methods 0.000 description 7
- 238000005406 washing Methods 0.000 description 6
- 229920005654 Sephadex Polymers 0.000 description 5
- 239000012507 Sephadex™ Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000000108 ultra-filtration Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 108700022849 desamido- insulin Proteins 0.000 description 3
- 235000013861 fat-free Nutrition 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012466 permeate Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000012675 alcoholic extract Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 239000004026 insulin derivative Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229920002492 poly(sulfone) Polymers 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000135 prohibitive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000004246 zinc acetate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
- C07K14/625—Extraction from natural sources
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1740/76A GB1581824A (en) | 1976-01-16 | 1976-01-16 | Preparation of insulin |
| GB1740/76 | 1976-01-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1112639A true CA1112639A (en) | 1981-11-17 |
Family
ID=9727172
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA269,730A Expired CA1112639A (en) | 1976-01-16 | 1977-01-14 | Mono-insulin and method of preparing the same |
Country Status (15)
| Country | Link |
|---|---|
| AT (2) | AT364717B (OSRAM) |
| AU (1) | AU514888B2 (OSRAM) |
| BE (1) | BE850387A (OSRAM) |
| CA (1) | CA1112639A (OSRAM) |
| DE (1) | DE2701092A1 (OSRAM) |
| DK (1) | DK14177A (OSRAM) |
| EG (1) | EG13113A (OSRAM) |
| ES (1) | ES455065A1 (OSRAM) |
| FI (1) | FI64508C (OSRAM) |
| FR (1) | FR2338250A1 (OSRAM) |
| GB (1) | GB1581824A (OSRAM) |
| IE (1) | IE45013B1 (OSRAM) |
| NL (1) | NL7700455A (OSRAM) |
| NO (2) | NO149875C (OSRAM) |
| SE (1) | SE445972B (OSRAM) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK311477A (da) * | 1977-07-08 | 1979-01-09 | Leo Lab | Fremgangsmaade ved fremstilling af rent insulin |
| US4459226A (en) * | 1982-02-26 | 1984-07-10 | Eli Lilly And Company | Process for recovering insulin |
| BG65045B1 (bg) * | 2001-12-03 | 2007-01-31 | "Софарма" Ад | Метод за получаване на високопречистен монокомпонентен инсулин |
| WO2012104339A1 (en) | 2011-02-01 | 2012-08-09 | Novo Nordisk A/S | Purification of insulin |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1966573C3 (de) * | 1969-08-07 | 1979-08-30 | Novo Terapeutisk Laboratorium A/S, Kopenhagen | Verfahren zur Reinigung von Insulin |
| GB1503919A (en) * | 1974-07-19 | 1978-03-15 | Leo Sa Lab | Recovery of insulin |
-
1976
- 1976-01-16 GB GB1740/76A patent/GB1581824A/en not_active Expired
-
1977
- 1977-01-10 AT AT0007977A patent/AT364717B/de not_active IP Right Cessation
- 1977-01-11 IE IE44/77A patent/IE45013B1/en unknown
- 1977-01-12 DE DE19772701092 patent/DE2701092A1/de not_active Withdrawn
- 1977-01-13 AU AU21317/77A patent/AU514888B2/en not_active Expired
- 1977-01-13 SE SE7700322A patent/SE445972B/xx unknown
- 1977-01-14 DK DK14177A patent/DK14177A/da not_active Application Discontinuation
- 1977-01-14 CA CA269,730A patent/CA1112639A/en not_active Expired
- 1977-01-14 BE BE174084A patent/BE850387A/xx not_active IP Right Cessation
- 1977-01-14 ES ES455065A patent/ES455065A1/es not_active Expired
- 1977-01-14 NO NO770119A patent/NO149875C/no unknown
- 1977-01-14 FR FR7701077A patent/FR2338250A1/fr active Granted
- 1977-01-14 FI FI770112A patent/FI64508C/fi not_active IP Right Cessation
- 1977-01-15 EG EG30/77A patent/EG13113A/xx active
- 1977-01-17 NL NL7700455A patent/NL7700455A/xx not_active Application Discontinuation
-
1980
- 1980-11-06 AT AT0546880A patent/AT366578B/de not_active IP Right Cessation
-
1982
- 1982-09-03 NO NO822985A patent/NO822985L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FI770112A7 (OSRAM) | 1977-07-17 |
| FI64508C (fi) | 1983-12-12 |
| FI64508B (fi) | 1983-08-31 |
| AU2131777A (en) | 1978-07-20 |
| NL7700455A (nl) | 1977-07-19 |
| NO770119L (no) | 1977-07-19 |
| FR2338250B1 (OSRAM) | 1980-04-04 |
| FR2338250A1 (fr) | 1977-08-12 |
| AU514888B2 (en) | 1981-03-05 |
| SE7700322L (sv) | 1977-07-17 |
| NO822985L (no) | 1977-07-19 |
| AT364717B (de) | 1981-11-10 |
| DK14177A (da) | 1977-07-17 |
| GB1581824A (en) | 1980-12-31 |
| SE445972B (sv) | 1986-08-04 |
| EG13113A (en) | 1983-03-31 |
| ATA7977A (de) | 1981-04-15 |
| NO149875B (no) | 1984-04-02 |
| ES455065A1 (es) | 1978-05-01 |
| DE2701092A1 (de) | 1977-07-28 |
| IE45013L (en) | 1977-07-16 |
| NO149875C (no) | 1984-07-11 |
| ATA546880A (de) | 1981-09-15 |
| IE45013B1 (en) | 1982-06-02 |
| AT366578B (de) | 1982-04-26 |
| BE850387A (fr) | 1977-05-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |