CH326787A - Procédé de fabrication de préparations injectables d'insuline à effet prolongé - Google Patents
Procédé de fabrication de préparations injectables d'insuline à effet prolongéInfo
- Publication number
- CH326787A CH326787A CH326787DA CH326787A CH 326787 A CH326787 A CH 326787A CH 326787D A CH326787D A CH 326787DA CH 326787 A CH326787 A CH 326787A
- Authority
- CH
- Switzerland
- Prior art keywords
- insulin
- zinc
- protamine
- sub
- solution
- Prior art date
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 description 94
- 102000004877 Insulin Human genes 0.000 title claims description 47
- 108090001061 Insulin Proteins 0.000 title claims description 47
- 229940125396 insulin Drugs 0.000 title claims description 47
- 238000000034 method Methods 0.000 title claims description 21
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 13
- 230000005923 long-lasting effect Effects 0.000 title description 3
- 229940048914 protamine Drugs 0.000 claims description 28
- 108010007568 Protamines Proteins 0.000 claims description 27
- 102000007327 Protamines Human genes 0.000 claims description 27
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 27
- 239000011701 zinc Substances 0.000 claims description 27
- 229910052725 zinc Inorganic materials 0.000 claims description 27
- 239000000243 solution Substances 0.000 claims description 19
- 239000000725 suspension Substances 0.000 claims description 17
- 102000005237 Isophane Insulin Human genes 0.000 claims description 14
- 108010081368 Isophane Insulin Proteins 0.000 claims description 14
- 239000000126 substance Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 7
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000012736 aqueous medium Substances 0.000 claims description 4
- 239000012928 buffer substance Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 239000007900 aqueous suspension Substances 0.000 claims description 3
- 239000000470 constituent Substances 0.000 claims description 3
- 150000003752 zinc compounds Chemical class 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 102000016261 Long-Acting Insulin Human genes 0.000 claims 1
- 108010092217 Long-Acting Insulin Proteins 0.000 claims 1
- 229940100066 Long-acting insulin Drugs 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000012153 distilled water Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000003637 basic solution Substances 0.000 description 7
- 239000011550 stock solution Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000011146 sterile filtration Methods 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108010040512 Clupeine Proteins 0.000 description 1
- 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 description 1
- 101100113998 Mus musculus Cnbd2 gene Proteins 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- XEBWQGVWTUSTLN-UHFFFAOYSA-M phenylmercury acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1 XEBWQGVWTUSTLN-UHFFFAOYSA-M 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940070353 protamines Drugs 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- RGHFKWPGWBFQLN-UHFFFAOYSA-M sodium;5,5-diethylpyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].CCC1(CC)C([O-])=NC(=O)NC1=O RGHFKWPGWBFQLN-UHFFFAOYSA-M 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK189153A DK87403C (da) | 1953-06-04 | 1953-06-04 | Fremgangsmåde til fremstilling af protraheret virkende, injicerbare insulinpræparater. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH326787A true CH326787A (fr) | 1957-12-31 |
Family
ID=8108845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH326787D CH326787A (fr) | 1953-06-04 | 1954-05-28 | Procédé de fabrication de préparations injectables d'insuline à effet prolongé |
Country Status (4)
| Country | Link |
|---|---|
| CH (1) | CH326787A (da) |
| DE (1) | DE977478C (da) |
| DK (1) | DK87403C (da) |
| GB (1) | GB751425A (da) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0265214A3 (en) * | 1986-10-20 | 1989-07-26 | Novo Nordisk A/S | Polypeptide preparation |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA808097B (en) * | 1980-12-29 | 1982-01-27 | Lilly Co Eli | Novel insulin formulations |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE835499C (de) * | 1945-05-17 | 1952-03-31 | Novo Terapeutisk Labor As | Verfahren zur Herstellung von Inselhormon in kristallinischer Form |
-
1953
- 1953-06-04 DK DK189153A patent/DK87403C/da active
-
1954
- 1954-05-27 DE DEN8968A patent/DE977478C/de not_active Expired
- 1954-05-28 CH CH326787D patent/CH326787A/fr unknown
- 1954-06-02 GB GB16365/54A patent/GB751425A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0265214A3 (en) * | 1986-10-20 | 1989-07-26 | Novo Nordisk A/S | Polypeptide preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| DE977478C (de) | 1966-08-04 |
| DK87403C (da) | 1959-06-08 |
| GB751425A (en) | 1956-06-27 |
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