CA1155439A - Insulin crystal suspension and process for the preparation thereof - Google Patents
Insulin crystal suspension and process for the preparation thereofInfo
- Publication number
- CA1155439A CA1155439A CA000358705A CA358705A CA1155439A CA 1155439 A CA1155439 A CA 1155439A CA 000358705 A CA000358705 A CA 000358705A CA 358705 A CA358705 A CA 358705A CA 1155439 A CA1155439 A CA 1155439A
- Authority
- CA
- Canada
- Prior art keywords
- insulin
- crystals
- pig
- crystal suspension
- suspension
- 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 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 84
- 239000013078 crystal Substances 0.000 title claims abstract description 59
- 108090001061 Insulin Proteins 0.000 title claims abstract description 35
- 102000004877 Insulin Human genes 0.000 title claims abstract description 35
- 229940125396 insulin Drugs 0.000 title claims abstract description 35
- 239000000725 suspension Substances 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 9
- 230000008569 process Effects 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title abstract description 6
- 230000009466 transformation Effects 0.000 claims abstract description 14
- 101000993800 Sus scrofa Insulin Proteins 0.000 claims abstract description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 28
- 239000011780 sodium chloride Substances 0.000 claims description 14
- 239000002609 medium Substances 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims description 4
- 230000003111 delayed effect Effects 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 2
- 239000011701 zinc Substances 0.000 abstract description 39
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 abstract description 13
- 229910052725 zinc Inorganic materials 0.000 abstract description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 12
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
- 239000001632 sodium acetate Substances 0.000 description 8
- 235000017281 sodium acetate Nutrition 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- 229940083608 sodium hydroxide Drugs 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 229910001868 water Inorganic materials 0.000 description 6
- 235000005074 zinc chloride Nutrition 0.000 description 6
- 239000011592 zinc chloride Substances 0.000 description 6
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 5
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 5
- 229960002216 methylparaben Drugs 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229960000443 hydrochloric acid Drugs 0.000 description 4
- 235000011167 hydrochloric acid Nutrition 0.000 description 4
- 229960005190 phenylalanine Drugs 0.000 description 4
- 238000007792 addition Methods 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 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
- 101001011741 Bos taurus Insulin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000861718 Chloris <Aves> Species 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
- 108700027570 Phe(B1)- insulin Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 238000002083 X-ray spectrum Methods 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound 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)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](CC=3NC=NC=3)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)=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(C)C)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)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000012928 buffer substance Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792933946 DE2933946A1 (de) | 1979-08-22 | 1979-08-22 | Insulinkristallsuspension und verfahren zu ihrer herstellung. |
| DEP2933946.6 | 1979-08-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1155439A true CA1155439A (en) | 1983-10-18 |
Family
ID=6079022
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000358705A Expired CA1155439A (en) | 1979-08-22 | 1980-08-21 | Insulin crystal suspension and process for the preparation thereof |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0025868B1 (en, 2012) |
| JP (1) | JPS5632412A (en, 2012) |
| AT (1) | ATE1281T1 (en, 2012) |
| AU (1) | AU539091B2 (en, 2012) |
| CA (1) | CA1155439A (en, 2012) |
| DE (2) | DE2933946A1 (en, 2012) |
| DK (1) | DK149347C (en, 2012) |
| ES (1) | ES494260A0 (en, 2012) |
| GR (1) | GR69915B (en, 2012) |
| IE (1) | IE50188B1 (en, 2012) |
| IL (1) | IL60889A (en, 2012) |
| ZA (1) | ZA805152B (en, 2012) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6294656B1 (en) | 1995-07-25 | 2001-09-25 | Novartis Corporation | Transforming growth factor β crystals |
| EP3908599A4 (en) * | 2019-01-10 | 2022-11-09 | Biocon Limited | PREPARATIVE CRYSTALLIZATION OF RECOMBINANT HUMAN INSULIN |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5534488A (en) * | 1993-08-13 | 1996-07-09 | Eli Lilly And Company | Insulin formulation |
| US5474978A (en) * | 1994-06-16 | 1995-12-12 | Eli Lilly And Company | Insulin analog formulations |
| US5504188A (en) * | 1994-06-16 | 1996-04-02 | Eli Lilly And Company | Preparation of stable zinc insulin analog crystals |
| YU18596A (sh) * | 1995-03-31 | 1998-07-10 | Eli Lilly And Company | Analogne formulacije monomernog insulina |
| ATE219942T1 (de) * | 1997-03-20 | 2002-07-15 | Novo Nordisk As | Therapeutische pulverformulierung zur pulmonaren anwendung, welche kristallines insulin enthält |
| DE102009001969A1 (de) | 2009-03-30 | 2010-10-07 | Robert Bosch Gmbh | Sensormodul |
-
1979
- 1979-08-22 DE DE19792933946 patent/DE2933946A1/de not_active Withdrawn
-
1980
- 1980-08-14 ES ES494260A patent/ES494260A0/es active Granted
- 1980-08-16 AT AT80104879T patent/ATE1281T1/de not_active IP Right Cessation
- 1980-08-16 EP EP80104879A patent/EP0025868B1/de not_active Expired
- 1980-08-16 DE DE8080104879T patent/DE3060628D1/de not_active Expired
- 1980-08-20 GR GR62708A patent/GR69915B/el unknown
- 1980-08-21 IL IL60889A patent/IL60889A/xx unknown
- 1980-08-21 DK DK359380A patent/DK149347C/da not_active IP Right Cessation
- 1980-08-21 AU AU61621/80A patent/AU539091B2/en not_active Ceased
- 1980-08-21 CA CA000358705A patent/CA1155439A/en not_active Expired
- 1980-08-21 IE IE1762/80A patent/IE50188B1/en unknown
- 1980-08-21 ZA ZA00805152A patent/ZA805152B/xx unknown
- 1980-08-22 JP JP11487980A patent/JPS5632412A/ja active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6294656B1 (en) | 1995-07-25 | 2001-09-25 | Novartis Corporation | Transforming growth factor β crystals |
| EP3908599A4 (en) * | 2019-01-10 | 2022-11-09 | Biocon Limited | PREPARATIVE CRYSTALLIZATION OF RECOMBINANT HUMAN INSULIN |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3060628D1 (en) | 1982-08-19 |
| DK359380A (da) | 1981-02-23 |
| IE50188B1 (en) | 1986-03-05 |
| GR69915B (en, 2012) | 1982-07-21 |
| DK149347C (da) | 1986-10-20 |
| IL60889A0 (en) | 1980-10-26 |
| IE801762L (en) | 1981-03-22 |
| ES8205752A1 (es) | 1982-08-01 |
| ATE1281T1 (de) | 1982-07-15 |
| ZA805152B (en) | 1981-08-26 |
| EP0025868B1 (de) | 1982-06-30 |
| EP0025868A1 (de) | 1981-04-01 |
| IL60889A (en) | 1983-07-31 |
| AU6162180A (en) | 1981-04-09 |
| JPS5632412A (en) | 1981-04-01 |
| AU539091B2 (en) | 1984-09-13 |
| DK149347B (da) | 1986-05-12 |
| DE2933946A1 (de) | 1981-03-12 |
| ES494260A0 (es) | 1982-08-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |